Amide compounds and use thereof

ABSTRACT

An amide compound given by formula [I]:                    
     wherein R 1  represents a C1-C10 haloalkyl and so on, R2 represents a hydrogen and so on, X represents an oxygen or sulfur, Y represents an oxygen or sulfur, Ar represents an aromatic group, A represents an ethylene and so on, and Z 1  and Z 2  represent alkyl, alkoxy and so on, and a fungicide containing it as an active ingredient.

This application is a 371 of PCT/JP01/05037, filed Jun. 13, 2001.

1. Technical Field

The present invention relates to amide compounds and their use forfungicide.

2. Background Arts

The present invention provides an amide compound which can be moreexcellent fungicidal active ingredient, though various fungicides forcontrolling plant diseases have been known hitherto.

DISCLOSURE OF THE INVENTION

The present invention provides an amide compound given by formula [I]:

wherein R¹ represents a C1-C10 haloalkyl group, C2-C10 haloalkenylgroup, C3-C10 haloalkynyl group, C3-C8 halocycloalkyl group or C3-C10alkynyl group; R² represents a hydrogen atom or C1-C3 alkyl group(namely, methy, ethyl, propyl and isopropyl); X represents an oxygenatom or sulfur atom; Y represents an oxygen atom or sulfur atom; Arrepresents an aromatic group; A represents an ethylene group ortrimethylene group, said ethylene group and trimethylene group may besubstituted by one or more selected from halogen atom, amino group,hydroxy group, cyano group, nitro group, C1-C6 alkyl group, C3-C6cycloalkyl group, C3-C6 cycloalkenyl group, C1-C6 alkoxy group, C1-C6haloalkoxy group, C1-C6 alkylthio group, C1-C6 haloalkylthio group,C2-C6 (alkoxycarbonyl) group and tri(C1-C6 alkyl)silyl group; Z¹ and Z²are the same or different and represents a halogen atom (chlorine,bromine, fluorine, iodine), C1-C6 alkyl group, C1-C6 haloalkyl group,C2-C6 alkenyl group, C2-C6 alkynyl group, C3-C6 cycloalkyl group, C1-C6alkoxy group, C1-C6 haloalkoxy group, C2-C6 (alkoxyalkoxy) group, C4-C6(cycloalkylalkoxy) group, C3-C6 alkenyloxy group, C3-C6 haloalkenyloxygroup, C3-C6 alkynyloxy group, C3-C6 haloalkynyloxy group, C3-C6cycloalkoxy group, C3-C6 cycloalkenyloxy group, cyano C1-C5 alkoxygroup, C1-C6 alkylthio group, C1-C6 haloalkylthio group (C1-C5alkoxy)carbonyl group, phenoxy group, benzyloxy group, hydroxy group orcyano group, the benzene ring of said phenyl group and benzyloxy groupmay be substituted by one or more selected from halogen atom (chlorine,bromine, fluorine, iodine) C1-C6 alkyl group, C1-C6 alkoxy group,trifluoromethyl group, amino group and nitro group; and Z¹ and Z² mayrepresents C2-C6 alkylenedioxy group together, (hereinafter, referred toas the present compound) and fungicide comprising it as an activeingredient.

In the present invention, examples of the C1-C10 haloalkyl group for R¹include fluoromethyl, difluoromethyl, trifluoromethyl,chlorodifluoromethyl, chlorofluoromethyl, bromodifluoromethyl,trichloromethyl, dichlorobromomethyl, 1,1,2,2,2-pentafluoroethyl,2,2,2-trifluoroethyl, 2,2-difluoroethyl and 2-fluoroethyl; examples ofthe C2-C10 haloalkenyl group include 2-fluorovinyl, 2,2-difluorovinul,trifluorovinyl, 3-chloropropenyl, 3,3-dichloropropenyl,3-fluoropropenyl, 3,3-difluoropropenyl, 2,3,3-trifluoropropenyl and10-fluoro-2-decenyl; examples of the C3-C10 haloalkynyl group include3-fluoro-2-propynyl, 3-chloro-2-propynyl, 3-bromo-2-propynyl,3-iodo-2-propynyl, 4-fluoro-2-butynyl, 4,4-difluoro-2-butynyl,4,4,4-trifluoro-2-butynyl and 4-chloro-2-butynyl; examples of the C3-C8halocycloalkyl group include 2,2-difluorocyclopropyl,2,3,4-trifluorocyclobutyl, 2,5-dichlorocyclopentyl,4,4-difluorocyclohexy and 2-chlorocycloheptyl; and examples of theC3-C10 alkynyl group include 2-propynyl, 2-butynyl, 3-butynyl,1-methyl-2-propynyl, 5-pentynyl and 7-octynyl. Among them, C1-C3haloalkyl group, C2-C3 haloalkenyl group, C3-C5-haloalkynyl group, C3-C6halocycloalkyl group and C3-C8 alkynyl group are preferable, andespecialy fluoromethyl, difluoromethyl, trifluoromethyl and 2-propynylare more preferable for R¹.

In the present invention, examples of the aromatic group for Ar includearomatic hydrocarbyl groups such as phenyl, naphthyl (1-naphthyl,2-naphthyl) and so on; and aromatic heterocyclic groups such as thienyl(2-thienyl, 3-thienyl), furyl (2-furyl, 3-furyl), pyrrolyl (1-pyrrolyl,2-pyrrolyl, 3-pyrrolyl), pyrazolyl (1-pyrazolyl, 3-pyrazolyl,4-pyrazolyl), imidazolyl (1-imidazolyl, 2-imidazolyl, 4-imidazolyl),triazolyl (1-triazolyl, 4-triazolyl), tetrazolyl (1-tetrazolyl,5-tetrazolyl), thiazolyl (2-thiazolyl, 4-thiazolyl, 5-thiazolyl),isothiazolyl (3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl), oxazolyl(2-oxazolyl, 4-oxazolyl, 5-oxazolyl), isoxazolyl (3-isoxazolyl,4-isoxazolyl, 5-isoxazolyl), thiadiazolyl (e.g. 1,2,5-thiadiazol-4-yl,1,3,4-thiadiazol-2-yl, 1,2,3-thiadiazol-5-yl), pyridyl (2-pyridyl,3-pyridyl, 4-pyridyl), pyrimidinyl (2-pyrimidinyl, 4-pyrimidinyl,5-pyrimidinyl), pyrazinyl, pyridazinyl (3-pyridazinyl, 4-pyridazinyl),benzofuryl (2-benzofuryl, 3-benzofuryl, 4-benzofuryl, 5-benzofuryl,6-benzofuryl, 7-benzofuryl), benzothienyl (2-benzothienyl,3-benzothienyl, 4-benzothienyl, 5-benzothienyl, 6-benzothienyl,7-benzothienyl), indolyl (1-indolyl, 2-indolyl, 3-indolyl, 4-indolyl,5-indolyl, 6-indolyl, 7-indolyl), benzothiazolyl (2-benzothiazolyl,4-benzothiazolyl, 5-benzothiazolyl, 6-benzothiazolyl, 7-benzothiazolyl),benzimidazolyl (1-benzimidazolyl, 2-benzimidazolyl, 4-benzimidazolyl,5-benzimidazolyl, 6-benzimidazolyl, 7-benzimidazolyl), benzopyrazolyl(1-benzopyrazolyl, 2-benzopyrazolyl, 3-benzopyrazolyl, 4-benzopyrazolyl,5-benzopyrazolyl, 6-benzopyrazolyl, 7-benzopyrazolyl), quinolyl(2-quinolyl, 3-quinolyl, 4-quinolyl, 5-quinolyl, 6-quinolyl, 7-quinolyl,8-quinolyl), isoquinolyl (1-isoquinolyl, 3-isoquinolyl, 4-isoquinolyl,5-isoquinolyl, 6-isoquinolyl, 7-isoquinolyl, 8-isoquinolyl),pyrazolopyrimidinyl, imidazopyrimidinyl, thiophenopyrimidinyl,thiazolopyrimidinyl, pyrazolopyridyl, imidazopyridyl, thiophenopyridyl,thiazolopyridyl and so on; and said aromatic hydrocarbyl group andaromatic heterocyclic group may be substituted. Typical examples of thesubstituents include halogen (chlorine, bromine, fluorine, iodine),amino, hydroxy, cyano, nitro, C1-C10 alkyl (e.g. methyl, ethyl, propyl,isopropyl, butyl, isobutyl, 1-methylpropyl, pentyl, 1-methylbutyl,1-ethylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl,1,2-dimethylbutyl, 1,1-dimethylpropyl, hexyl, 1-methylpentyl,1-ethylpentyl, 3,3-dimethylbutyl, heptyl, 3,7-dimethyloctyl), C1-C10haloalkyl (e.g. trifluoromethyl, 2,2,2-trifluoroethyl,1,1,2,2-tetrafluoroethyl), cyano C1-C9 alkyl (e.g. cyanomethyl,1-cyanoethyl, 2-cyanoethyl, 3-cyanopropyl, 5-cyanohexyl), C2-C10 alkenyl(e.g. vinyl, 1-propenyl, 2-propenyl, 1-methyl-1-propenyl, 1-butenyl,2-butenyl, 3-butenyl, 3,3-dimethyl-1-butenyl, 4-pentenyl, 5-hexenyl),C2-C10 haloalkenyl (e.g. 2-fluorovinyl, 3-chloro-2-propenyl,3,3-dichloro-2-propenyl, 2-fluoro-1-propenyl,3,3,3-trifluoro-1-propenyl, 4-chloro-3-butenyl,2-chloro-3-methyl-1-butenyl, 2-fluoro-5-hexenyl), C2-C10 alkynyl (e.g.ethynyl, 1-propynyl, 2-propynyl, 1-methyl-2-propynyl,1-ethyl-2-propynyl, 1-butynyl, 3,3-dimethyl-1-butynyl, 3-butynyl,4-pentynyl, 5-hexynyl), C2-C10 haloalkynyl (e.g. 2-fluoroethynyl,2-chloroethynyl, 3-chloro-2-propynyl, 4-fluoro-3-butynyl,5-chloro-4-pentynyl, 6-bromo-5-hexynyl), C3-C6 cycloalkyl (e.g.cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl), C3-C6 cycloalkenyl(e.g. 2-cyclopentenyl, 2-cyclohexenyl), C1-C10 alkoxy (e.g. methoxy,ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy, isobutoxy, pentyloxy),C1-C10 haloalkoxy (e.g. trifluoromethoxy, difluoromethoxy,bromodifluoromethoxy, chlorodifluoromethoxy, fluoromethoxy,2,2,2-trifluoroethoxy, 1,1,2,2-tetrafluoroethoxy), C3-C10 alkenyloxy(e.g. 2-propenyloxy, 1-methyl-2-propenyloxy, 1-ethyl-2-propenyloxy,2-butenyloxy, 3-butenyloxy, 2,2-dimethyl-3-butenyloxy, 4-pentenyloxy,5-hexenyloxy), C3-C10 haloalkenyloxy (e.g. 3-chloro-2-propenyloxy,3,3-dichloro-2-propenyloxy, 2-fluoro-1-propenyloxy,3,3,3-trifluoro-1-propenyloxy, 4-chloro-3-butenyloxy,2-chloro-3-methyl-1-butenyloxy, 2-fluoro-5-hexenyloxy), C3-C10alkynyloxy (e.g. 2-propynyloxy, 1-methyl-2-propynyloxy,1-ethyl-2-propynyloxy, 2-butynyloxy, 3-butynyloxy, 4-pentynyloxy,5-hexynyloxy), C3-C10 haloalkynyloxy (e.g. 3-chloro-2-propynyloxy,3-fluoro-2-propynyloxy, 4-fluoro-3-butynyloxy, 5-chloro-4-pentynyloxy,6-bromo-5-hexynyloxy), C3-C10 cycloalkoxy (e.g. cyclopropoxy,cyclobutoxy, cyclopentyloxy, cyclohexyloxy, cyclooctyloxy), cyano C1-C9alkoxy (e.g. cyanomethoxy, 1-cyanoethoxy, 2-cyanoethoxy, 3-cyanopropoxy,5-cyanohexyloxy), C1-C10 alkylthio (e.g. methylthio, ethylthio,propylthio, butylthio, isobutylthio, sec-butylthio, pentylthio,hexylthio), C1-C10 haloalkylthio (e.g. trifluoromethylthio,difluoromethylthio, bromodifluoromethylthio, chlorodifluoromethylthio,fluoromethylthio, 2,2,2-trifluoroethylthio,1,1,2,2-tetrafluoroethylthio), C2-C10 (alkoxycarbonyl) (e.g.methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl,butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl,pentyloxycarbonyl, hexyloxycarbonyl), tri(C1-C6 alkyl)silyl (e.g.trimethylsilyl, triethylsilyl), C3-C5 alkylene (e.g. trimethylene,tetramethylene, pentamethylene) and methylenedioxy. Among them,preferred Ar's are 4-methylphenyl group, 4-ethylphenyl group,4-methoxyphenyl group, 4-chlorophenyl group, 4-trifluoromethylphenylgroup, 3,4-tetramethylenephenyl group (5,6,7,8-tetrahydronaphthalen-2-ylgroup), 3,4-trimethylenephenyl group (indan-5-yl group) and 2-naphthylgroup.

In the present invention, the ethylene group (—CH₂CH₂—) and trimethylenegroup for A may be substituted by at least one selected from halogen(chlorine, bromine, fluorine, iodine), amino, hydroxy, cyano, nitro,C1-C6 alkyl (e.g. methyl, ethyl, propyl, isopropyl, butyl, sec-butyl,isobutyl, t-butyl), C3-C6 cycloalkyl (e.g. cyclopropyl, cyclopentyl,cyclohexyl), C3-C6 cycloalkenyl, C1-C6 alkoxy (e.g. methoxy, ethoxy,propoxy, isopropoxy, butoxy, sec-butoxy, isobutoxy, pentyloxy), C1-C6haloalkoxy (e.g. trifluoromethoxy, difluoromethoxy,bromodifluoromethoxy, chlorodifluoromethoxy, fluoromethoxy,2,2,2-trifluoroethoxy, 1,1,2,2-tetrafluoroethoxy), C1-C6 alkylthio (e.g.methylthio, ethylthio, propylthio, butylthio, isobutylthio,sec-butylthio, pentylthio, hexylthio), C1-C6 haloalkylthio (e.g.trifluoromethylthio, difluoromethylthio, bromodifluoromethylthio,chlorodifluoromethylthio, fluoromethylthio, 2,2,2-trifluoroethylthio,1,1,2,2-tetrafluoroethylthio), C2-C6 (alkoxycarbonyl) (e.g.methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl,butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl,pentyloxycarbonyl, hexyloxycarbonyl) and (C1-C6 alkyl)silyl (e.g.trimethylsilyl, triethylsilyl). Among them, ethylene (—CH₂CH₂—) ispreferable for A.

In the present invention, examples of the C1-C6 alkyl group for Z¹ andZ² include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl,pentyl, 1-methylbutyl, 1-ethylbutyl, 2-methylbutyl, 3-methylbutyl,2,2-dimethylpropyl, 1,2-dimethylpropyl, 1,1-dimethylpropyl, hexyl,1-methylpentyl and 3,3-dimethylbutyl; examples of the C1-C6 haloalkylgroup include trifluoromethyl, 2,2,2-trifluoroethyl and1,1,2,2-tetrafluoroethyl; examples of the C2-C6 alkenyl group includevinyl, 2-propenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl, 2-butenyl,3-butenyl, 3-methyl-2-butenyl, 4-methyl-3-butenyl, 4-pentenyl and5-hexenyl; C2-C6 alkynyl group include ethynyl, 2-propynyl,1-methyl-2-propynyl, 1-ethyl-2-propynyl, 2-butynyl, 3-butynyl,1-methyl-2-butynyl, 2-pentynyl and 4,4-dimethyl-2-pentynyl; examples ofthe C3-C6 cycloalkyl group include cyclopropyl, cyclopentyl andcyclohexyl; examples of the C1-C6 alkoxy group include methoxy, ethoxy,propoxy, isopropoxy, butoxy, sec-butoxy, isobutoxy and pentyloxy;examples of the C1-C6 haloalkoxy group include trifluoromethoxy,difluoromethoxy, bromodifluoromethoxy, chlorodifluoromethoxy,fluoromethoxy, 2,2,2-trifluoroethoxy and 1,1,2,2-tetrafluoroethoxy;examples of the C2-C6 (alkoxyalkoxy) group include methoxymethoxy,2-methoxyethoxy, ethoxymethoxy and isopropoxymethoxy; examples of theC4-C6 (cycloalkylalkoxy) group include cyclopropylmethyl; examples ofthe C3-C6 alkenyloxy group include 2-propenyloxy,1-methyl-2-propenyloxy, 2-methyl-2-propenyloxy, 2-butenyloxy,3-butenyloxy, 3-methyl-2-butenyloxy, 4-methyl-3-butenyloxy,4-pentenyloxy and 5-hexenyloxy; examples of the C3-C6 haloalkenyloxygroup include 2-chloro-2-propenyloxy, 3-fluoro-2-propenyloxy,3-chloro-2-propenyloxy, 3-bromo-2-propenyloxy,3,3-dichloro-2-propenyloxy, 2,3, 3-trifluoro-2-propenyloxy,4-chloro-2-butenyloxy, 4-chloro-3-butenyloxy and 3-chloro-3-butenyloxy;examples of the C3-C6 alkynyloxy group include 2-propynyloxy,1-methyl-2-propynyloxy, 1-ethyl-2-propynyloxy, 2-butynyloxy,3-butynyloxy, 1-methyl-2-butynyloxy, 2-pentynyloxy, 4-pentynyloxy and4,4-dimethyl-2-pentynyloxy; examples of the C3-C6 haloalkynyloxy groupinclude 3-fluoro-2-propynyloxy, 3-chloro-2-propynyloxy,3-bromo-2-propynyloxy, 3-chloro-1-methyl-2-propynyloxy,4,4,4-trifluoro-2-butynyloxy, 4-chloro-3-butynyloxy and5-chloro-4-pentynyloxy; examples of the C3-C6 cycloalkoxy group includecyclopropoxy, cyclopentyloxy and cyclohexyloxy; examples of the C3-C6cycloalkenyloxy group include cyclopentenyloxy and cyclohexenyloxy;examples of the cyano C1-C5 alkoxy group include cyanomethoxy,1-cyanoethoxy and 2-cyanoethoxy; examples of the C1-C6 alkylthio groupinclude methylthio, ethylthio, propylthio, butylthio, isobutylthio,sec-butylthio, pentylthio and hexylthio; examples of the C1-C6haloalkylthio group include trifluoromethylthio, difluoromethylthio,bromodifluoromethylthio, chlorodifluoromethylthio, fluoromethylthio,2,2,2-trifluoroethylthio and 1,1,2,2-tetrafluoroethylthio; examples ofthe (C1-C5 alkoxy)carbonyl group include methoxycarbonyl,ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl,isobutoxycarbonyl, sec-butoxycarbonyl and pentyloxycarbonyl; examples ofthe optionally substituted phenoxy group include phenoxy,4-chlorophenoxy, 4-methylphenoxy, 4-methoxyphenoxy and4-trifluoromethylphenoxy; examples of the optionally substitutedbenzyloxy group include benzyloxy, 4-chlorobenzyloxy, 4-methylbenzyloxy,4-methoxybenzyloxy and 4-trifluoromethylbenzyloxy; and examples of theC2-C6 alkylenedioxy group include ethylenedioxy, propylenedioxy andtrimethylenedioxy. Among them, preferable are methoxy for Z¹ and methoxyand 2-propynyloxy for Z².

In the present compounds, there exist (E) and (Z) isomers based on C═Cdouble bond bonded with Ar and X, and the present invention include eachisomer and mixtures thereof.

In the present compounds, the compounds having excellent efficacy forcontrolling plant diseases are exemplified byN-[2-(3,4-dimethoxyphenyl)ethyl]-3-difluoromethoxy-2-(4-methylphenyl)acrylamide,N-[2-(3,4-dimethoxyphenyl)ethyl]-3-difluoromethoxy-2-[2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide,N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-3-difluoromethoxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide,N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-3-difluoromethoxy-2-(4-methylphenyl)acrylamide,N-[2-(3,4-dimethoxyphenyl)ethyl]-3-difluoromethoxy-2-(4-chlorophenyl)acrylamideandN-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-3-difluoromethoxy-2-(4-chlorophenyl)acrylamide.

The present compounds can be produced, for example, by the following[Production method A], [Production method B] or [Production method C].In these production methods, a protective group may be utilized forprotecting a functional group from chemical reaction, if necessary.

Production Method A

Production method of making the compound given by formula [II] to reactwith the compound given by formula [III]

In the above scheme, L¹ represents a leaving group such as chlorine,bromine, iodine, p-toluenesulfonyloxy, methanesulfonyloxy andtrifluoromethanesulfonyl; R¹¹ represents C1-C10 haloalkyl group such asfluoromethyl, difluoromethyl, bromodifluoromethyl and fluoroethoxy,C3-C10 haloalkenyl group such as 3,3-dichloroally or C3-C10 haloalkynylgroup such as 2-propynyl; and R², X, Y, Ar, A, Z¹ and Z² have the samemeanings as defined above.

Step 1 (process 1) in the above scheme is a process for producing thepresent compound given by formula [I-1] by making the compound given byformula [II] react with the compound given by formula [III] optionallyin the presence of a base. The reaction temperature is usually in therange of 0-100° C. and the reaction period is usually in the range of1-24 hours. The amount of the compound given by formula [III] utilizedfor the reaction is usually 0.5-10 mols, preferably 1-3 mols based on 1mol of the compound given by formula [II].

When the base is utilized for the reaction, the amount of the base isusually 1-10 mols moles based on 1 mol of the compound given by formula[II]. Examples of the base include inorganic bases such as sodiumhydroxide, potassium hydroxide, sodium carbonate, potassium carbonate,sodium hydride and the like; organic bases such as pyridine,triethylamine, ethyldiisopropylamine and the like; and mixtures thereof.

The reaction is usually carried out in a solvent. Examples of thesolvent include ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycol dimethyl ether and t-butyl methyl ether; aliphatic hydrocarbonssuch as hexane and heptane; aromatic hydrocarbons such as toluene;halogenated hydrocarbons such as chlorobenzene; organic bases such aspyridine, triethylamine and N,N-dimethylaniline; esters such as butylacetate and ethyl acetate; nitrites such as acetonitrile;N,N-dimethylformamide; dimethyl sulfoxide; water; and mixtures thereof.

The reaction solution after the reaction is subjected to usual work-upsuch as extraction with organic solvent, concentration and so on toprovide the isolated objective product. The objective product can bepurified by recrystallization, distillation, chromatography and so on.

The compound given by formula [I] wherein R¹ is trifluoromethyl can beprepared according to the methods described in Tetrahydron Lett., 1973,2253 and J. Org. Chem., 1979, 44, 3872. At that time, Production Example15 given below can be comferred.

The compound given by formula [II] wherein X is oxygen and Y is alsooxygen (the compound given by formula [II-1] in the scheme below) can beprepared according to the methods described in Chem. Ber., 1971, 104,2709, J. Org. Chem., 1966, 61, 3358 and Adv. Heterocycl. Chem., 1981,31, 207. It can be concretely produced according to the followingscheme.

In the above scheme, L³ and L⁴ are the same or different and representalkoxy group such as t-butoxy group; L² represents chlorine or bromineatom; and R², Ar A, Z¹ and Z² have the same meanings as defined above.

The step 2-1 is a step of making the compound given by formula [IV]react with the compound given by formula [V] in the presence of a baseto provide the compound given by formula [VI]. The reaction temperatureis usually in the range of 0 to 100° C. and the amount of the compoundgiven by formula [V] is usually 1 to 5 mols based on 1 mol of thecompound given by formula [IV].

The amount of the base used for the reaction is usually 1 to 10 molsbased on 1 mol of the compound given by formula [IV]. Examples of thebase include inorganic bases such as sodium hydroxide, potassiumhydroxide, sodium carbonate, potassium carbonate and sodium hydride;organic bases such as pyridine, triethylamine and ethyldiisopropylamine;and mixtures thereof.

The reaction is usually carried out in a solvent and examples of thesolvent include ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycol dimethyl ether and t-butyl methyl ether; aliphatic hydrocarbonssuch as hexane and heptane; aromatic hydrocarbons such as toluene;halogenated hydrocarbons such as chlorobenzene; organic bases such aspyridine, triethylamine and N,N-dimethylaniline; esters such as butylacetate and ethyl acetate; nitrites such as acetonitrile;N,N-dimethylformamide; dimethyl sulfoxide; water; and mixtures thereof.

The reaction solution after the reaction is subjected to usual work-upsuch as extraction with organic solvent, concentration and so on toprovide the isolated objective product. The objective product can bepurified by recrystallization, distillation, chromatography and so on.

The step 2-2 is a step of making the compound given by formula [VI]react with the compound given by formula [VII-1] or formula [VII-2] toprovide the compound given by formula [VIII]. The reaction temperatureis usually in the range of 50 to 150° C., the reaction period is usuallyin the range of 1 to 24 hours and the amount of the compound given byformula [VII-1] or formula [VII-2] is usually 1 to 10 mols based on 1mol of the compound given by formula [VI].

The reaction is usually carried out in a solvent and examples of thesolvent include ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycol dimethyl ether and t-butyl methyl ether; aliphatic hydrocarbonssuch as hexane and heptane; aromatic hydrocarbons such as toluene;halogenated hydrocarbons such as chlorobenzene; organic bases such aspyridine, triethylamine and N,N-dimethylaniline; nitrites such asacetonitrile; N,N-dimethylformamide; dimethyl sulfoxide; and mixturesthereof.

The reaction solution after the reaction is subjected to usual work-upsuch as extraction with organic solvent, concentration and so on toprovide the isolated objective product. The objective product can bepurified by recrystallization, distillation, chromatography and so on.

The step 2-3 is a step of making the compound given by formula [VIII]react with excess water in the presence of an acid to provide thecompound given by formula [II-1]. The reaction temperature is usually inthe range of 0 to 100° C. and examples of the acid include hydrochloricacid, sulfuric acid and p-toluenesulfonic acid. The amount of the acidis usually 0.1 to 100 mols based on 1 mol of the compound given byformula [VIII].

The reaction can be carried out in a solvent and examples of the solventinclude ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycoldimethyl ether and t-butyl methyl ether; aliphatic hydrocarbons such ashexane and heptane; aromatic hydrocarbons such as toluene; halogenatedhydrocarbons such as chlorobenzene; nitriles such as acetonitrile;N,N-dimethylformamide; dimethyl sulfoxide; and mixtures thereof.

The reaction solution after the reaction is subjected to usual work-upsuch as extraction with organic solvent, concentration and so on toprovide the isolated objective product. The objective product can bepurified by recrystallization, distillation, chromatography and so on.

Production Method B

Production method of making the compound given by formula [I-1] to reactwith 2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulfide(hereinafter, referred to as Lawesson's Reagent)

In the above scheme, R¹, R², X, Ar, A, Z¹ and Z² have the same meaningsas defined above.

The step 3 is a step of making the compound given by formula [I-1] reactwith Lawesson's Reagent in a solvent to provide the compound given byformula [I-2]. The reaction temperature is usually in the range of 50 to150° C. and the amount of the Lawesson's Reagent is usually 1 to 10 molsbased on 1 mol of the compound given by formula [I-1].

Examples of the solvent used for the reaction include ethers such as1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether and t-butylmethyl ether; aliphatic hydrocarbons such as hexane and heptane;aromatic hydrocarbons such as toluene; halogenated hydrocarbons such aschlorobenzene; organic bases such as pyridine, triethylamine andN,N-dimethylaniline; nitriles such as acetonitrile;N,N-dimethylformamide; dimethyl sulfoxide; and mixtures thereof.

The reaction solution after the reaction is subjected to usual work-upsuch as extraction with organic solvent, concentration and so on toprovide the isolated objective product. The objective product can bepurified by recrystallization, distillation, chromatography and so on.

Production Method C

Production method of making the compound given by formula [IX] to reactwith the compound given by formula [X]

In the above scheme, L⁵ represents p-toluenesulfonyl, methanesulfonyl ortrifluoromethanesulfonyl, and R¹, R², Y, Ar, A, Z¹ and Z² have the samemeanings as defined above.

The step 4 is a step of making the compound given by formula [IX] reactwith the compound given by formula [X]optionally in the presence of abase to provide the present compound given by formula [I]. The reactiontemperature is usually in the range of 0 to 100° C., the reaction periodis usually in the range of 1 to 24 hours and the amount of the compoundgiven by formula [X] is usually 0.5 to 10 mols, preferably 1 to 3 molsbased on 1 mol of the compound given by formula [IX].

When the base is utilized in the above reaction, the amount of the baseis usually 1 to 10 mols based on 1 mol of the compound given by formula[X]. Examples of the base include inorganic bases such as sodiumhydroxide, potassium hydroxide, sodium carbonate, potassium carbonateand sodium hydride; organic bases such as pyridine, triethylamine andethyldiisopropylamine; and mixtures thereof.

The reaction is usually carried out in a solent and examples of thesolvent include ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycol dimethyl ether and t-butyl methyl ether; aliphatic hydrocarbonssuch as hexane and heptane; aromatic hydrocarbons such as toluene;halogenated hydrocarbons such as chlorobenzene; organic bases such aspyridine, triethylamine and N,N-dimethylaniline; esters such as butylacetate and ethyl acetate; nitriles such as acetonitrile;N,N-dimethylformamide; dimethyl sulfoxide; water; and mixtures thereof.

The reaction solution after the reaction is subjected to usual work-upsuch as extraction with organic solvent, concentration and so on toprovide the isolated objective product. The objective product can bepurified by recrystallization, distillation, chromatography and so on.

The compound given by formula [IX] can be, for example, producedaccording to the following scheme.

In the above scheme, L⁵, R², Ar, A, Z¹ and Z² have the same meanings asdefined above.

The step 5 is a step of making the compound given by formula [II-1]react with the compound given by formula [X]optionally in the presenceof a base to provide the present compound given by formula [IX]. Thereaction temperature is usually in the range of −20 to 100° C., thereaction period is usually in the range of 1 to 24 hours and the amountof the compound given by formula [XI] is usually 0.5 to 10 mols,preferably 1 to 3 mols based on 1 mol of the compound given by formula[IX].

When the base is utilized in the above reaction, the amount of the baseis usually 1 to 10 mols based on 1 mol of the compound given by formula[II-1]. Examples of the base include inorganic bases such as sodiumhydroxide, potassium hydroxide, sodium carbonate, potassium carbonateand sodium hydride; organic bases such as pyridine, triethylamine andethyldiisopropylamine; and mixtures thereof.

The reaction is usually carried out in a solent and examples of thesolvent include ethers such as 1,4-dioxane, tetrahydrofuran, ethyleneglycol dimethyl ether and t-butyl methyl ether; aliphatic hydrocarbonssuch as hexane and heptane; aromatic hydrocarbons such as toluene;halogenated hydrocarbons such as chlorobenzene; organic bases such aspyridine, triethylamine and N,N-dimethylaniline; esters such as butylacetate and ethyl acetate; nitriles such as acetonitrile;N,N-dimethylformamide; dimethyl sulfoxide; water; and mixtures thereof.

The reaction solution after the reaction is subjected to usual work-upsuch as extraction with organic solvent, concentration and so on toprovide the isolated objective product. The objective product can bepurified by recrystallization, distillation, chromatography and so on.

The compound given by formula [IV] can be, for example, producedaccording to the following scheme.

wherein L² and Ar mean as described above.

The compound given by formula [XII] can be produced according to thedescription in Syn. Commun., 1982, 21, 415, JP sho58-41862A, TetrahedronLett., 1980,21,2547, Syn. Commun., 1976, 6, 349 and J. Am. Chem. Soc.,1977, 99, 4833.

The compound given by formula [V] can be produced according to thedescription in Bull. Chem. Soc, Jpn., 1990, 63, 1252, J. Am. Chem. Soc.,1955, 77, 2544, Synthesis, 1975, 590 and Chem. Lett., 1984, 1733.

When the present compound is used as an active ingredient of fungicide,it can be used as it is without any other ingredient, but it is usuallyformulated to emulsifiable concentrates, wettable powders, waterdispersible granules, emulsion formulations, flowables, dusts, granulesand so on by mixing with solid carrier, liquid carrier, surfactant orthe other auxiliaries and used. These formulations usually contain 0.1to 90% by weight of the present compound.

Examples of the solid carrier utilized for the formulation include finepowders or granules of minerals such as kaolin clay, attapulgite clay,bentonite, montmorillonite, terra alba, pyrophilite, talc, diatomaceousearth and calcite; natural organic substances such as corncob and walnutshell; synthetic organic substances such as urea; salts such as calciumcarbonate and ammonium sulfate; and synthetic inorganic substances suchas synthetic hydrous silicon oxide. Examples of the liquid carrierinclude aromatic hydrocarbons such as xylene, alkylbenzene andmethylnaphthalene; alcohols such as isopropanol, ethylene glycol,propylene glycol and cellosolve; ketones such as acetone, cyclohexanoneand isophorone; vegetable oils such as soybean oil and cottonseed oil;paraffin type aliphatic hydrocarbons; esters; dimethyl sulfoxide;acetonitrile and water.

Examples of the surfactant include anionic surfactants such asalkylsulfate ester salts, alkylarylsulfonate salts, dialkylsulfosaccinate salts, polyoxyethylenealkylary ether phosphate salts,ligninsulfonate salts and naphthalenesulfonate formaldehyde condensate;nonionic surfactants such as polyoxyethylenealkylary ether,polyoxyethylenealkylpolyoxypropylene block copolymers and sorbitan fattyacid esters.

Examples of the auxiliaries for formulation include water solublepolymers such as polyvinyl alcohol and polyvinylpyrrolidone;polysaccharides such as gum arabic, algin acid and its salts,CMC(carboxymethylcellulose) and xanthan gum; inorganic substances suchas alminium magnesium silicate and almina sol; preservatives; coloringagent; PAP (isopropyl acid phosphate) and stabilizers such as BHT.

The application methods of the present compounds are typically foliarapplication and soil treatment.

When the present compound is used for controlling plant diseases, thedosage is usually 1 to 5000 g, preferably 5 to 1000 g per 1 hectarethough it is variable depending on the type of plants (e.g. crops) to betreated, type of diseases to be controlled, degree of affection by thediseases, formulation type, application method, time of application,weather conditions and so on.

In case emulsifiable concentrates, wettable powders, flowables and thelike are used as aqueous dilution, the concentration of the activeingredient is 0.0001 to 3% by weight, preferably 0.0005 to 1% by weight.Dusts, granules and the like are applied as they are without dilution.The present compound is also used for the other known applicationmethods such as seed treatment. When it is used for seed treatment,seeds are usually soaked in 1 to 1000 ppm dilution of the presentcompound, or said dilution is sprayed to or daubed on the seeds.Further, dusts containing 0.1 to 10% by weight of the present compoundmay be applied by powder treatment.

The present compound can be used as agricultural/horticultural fungicidefor controlling plant diseases in the plowed fields, paddy fields,orchards, tea plantations, pastures, lawns and the like. Also, anincreased fungicidal effect can be expected by using the compounds inadmixture with other fungicides. Examples of such admixable otherfungicide include azole type fungicidal compounds such as propiconazole,triadimenol, prochloraz, penconazole, tebuconazole, flusilazole,diniconazole, bromconazole, epoxyconazole, diphenoconazole,ciproconazole, metoconazole, triflumizole, tetraconazole, microbutanil,fenbuconazole, hexaconazole, fluquinconazole, triticonazole, bitertanol,imazalil and flutriafol; cyclic amine type fungicidal compounds such asfenpropimorph, tridemorph and fenpropidin; benzimidazole type fungicidalcompounds such as carbendazim, benomyl, thiabendazole andthiophanate-methyl; procymidone; cyprodinil; pyrimethanil;diethofencarb; thiuram; fluazinam; mancozeb; iprodione; vinclozolin;chlorothalonil; captan; mepanipyrim; fenpiclonil; fludioxonil;dichlofluanide; folpet; kresoxim-methyl; azoxystrobin; trifloxystrobin;picoxystrobin; pyraclostrobin;N-methyl-α-ethoxyimino-2-[(2,5-dimethylphenoxy) methyl]phenylactamide,spiroxamine; quinoxyfen; phenhexamid; famoxadone; fenamidon (RP-407213)and iprovalicarb.

The present compound can be used in combination with otheragricultural/horticultural insecticides, acaricides, nematocides,herbicides, plant growth regulators and fertilizers. In the combination,they can be mixed in advance.

Examples of the insecticide, acaricide and nematocide includeorganophosphorus compounds such as fenitrothion [O,O-dimethylO-(3-methyl-4-nitrophenyl) phosphorothioate], fenthion [O,O-dimethylO-(3-methyl-4-(methythio)phenyl) phosphorothioate], diazinon[O,O-diethyl O-2-isopropyl-6-methylpyrimidin-4-yl phosphorothioate],chlorpyrifos [O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphorothioate],acephate [O,S-dimethyl acetylphosphoramidothioate], methidathion[S-2,3-dihydro-5-methoxy-2-oxo-1,3,4-thiadiazol-3-ylmethyl O,O-dimethylphosphorodithioate], disulfoton [O,O-diethyl S-2-ethylthioethylphosphorodithioate], DDVP [2,2-dichlorovinyl dimethyl phosphate],sulprofos [O-ethyl O-4-(methylthio)phenyl S-propyl phosphorodithioate],cyanophos [O-4-cyanophenyl O,O-dimethyl phosphorothioate], dioxabenzofos[2-methoxy-4H-1,3,2-benzodioxaphosphorin 2-sulfide], dimethoate[O,O-dimethyl S-(N-methylcarbamoylmethyl) dithiophosphate], phenthoate[ethyl 2-dimethoxyphosphinothioylthio(phenyl) acetate], malathion[diethyl (dimethoxyphosphinothioylthio) succinate], trichlorfon[dimethyl 2,2,2-trichloro-1-hydroxyethylphosphonate], azinphos-methyl[S-3,4-dihydro-4-oxo-1,2,3-benzotriazin-3-ylmethyl O,O-dimethylphosphorodithioate], monocrotophos [dimethyl(E)-1-methyl-2-(methylcarbamoyl) vinyl phosphate], ethion[O,O,O′,O′-tetraethyl S,S′-methylene bis (phosphorodithioate)] andfosthiazate [N-(O-methyl-S-sec-butyl) phosphorylthiazolidin-2-one];carbamate compounds such as BPMC [2-sec-butylphenyl methylcarbamate],benfracarb [ethylN-[2,3-dihydro-2,2-dimethylbenzofuran-7-yloxycarbonyl(methyl)aminothio]-N-isopropyl-β-alaninate],propoxur [2-isopropoxyphenyl N-methylcarbamate], carbosulfan[2,3-dihydro-2,2-dimethyl-7-benzo [b]furanylN-dibuthylaminothio-N-methylcarbamate], carbaryl [1-naphthylN-methylcarbamate], methomyl [S-methylN-[(methylcarbamoyl)oxy]thioacetimidate], ethiofencarb[2-(ethylthiomethyl) phenyl methylcarbamate], aldicarb[2-methyl-2-(methylthio)propionaldehyde O-methylcarbamoyloxime], oxamyl[N,N-dimethyl-2-methylcarbamoyloxyimino-2-(methylthio)acetamide] andfenothiocarb [S-4-phenoxybuthyl N,N-dimethylthiocarbamate]; pyrethroidcompounds such as etofenprox [2-(4-ethoxyphenyl)-2-methylpropyl3-phenoxybenzyl ether], fenvalerate [(RS)-α-cyano-3-phenoxybenzyl(RS)-2-(4-chlorophenyl)-3-methylbutyrate], esfenvalerate[(S)-α-cyano-3-phenoxybenzyl (S)-2-(4-chlorophenyl)-3-methylbutyrate],fenpropathrin [(RS)-α-cyano-3-phenoxybenzyl2,2,3,3-tetramethylcyclopropanecarboxylate], cypermethrin[(RS)-α-cyano-3-phenoxybenzyl (1RS,3RS)-3-(2,2-dichlorovinyl)-2,2-dimethyl-cyclopropanecarboxylate],permethrin [3-phenoxybenzyl(1RS,3RS)-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate],cyhalothrin [(RS)-α-cyano-3-phenoxybenzyl(Z)-(1RS,3RS)-3-(2-chloro-3,3,3-trifluoropropenyl)-2,2-dimethylcyclopropanecarboxylate],deltamethrin [(S)-α-cyano-m-phenoxybenzyl(1R,3R)-3-(2,2-dibromovinyl)-2,2-dimethyl-cyclopropanecarboxylate],cycloprothrin [(RS)-α-cyano-3-phenoxybenzyl(RS)-2,2-dichloro-1-(4-ethoxyphenyl)cyclopropanecarboxylate],fluvalinate [α-cyano-3-phenoxybenzylN-(2-chloro-α,α,α-trifluoro-p-tolyl)-D-valinate], bifenthrin[2-methylbiphenyl-3-ylmethyl(Z)-(1RS)-cis-3-(2-chloro-3,3,3-trifluoroprop-1-enyl)-2,2-dimethyl-cyclopropanecarboxylate]acrinathrin[cyano(3-phenoxyphenyl)methyl (1R-{1α(S*),3α(Z)})-2,2-dimethyl-3-[3-oxo-3-(2,2,2-trifluoro-1-(trifluoromethyl)ethoxy-1-propenyl)cyclopropanecarboxylate],2-methyl-2-(4-bromodifluoromethoxyphenyl) propyl 3-phenoxybenzyl ether,tralomethrin [(S)-α-cyano-3-phenoxybenzyl (1R-cis)3-(1,2,2,2-tetrabromoethyl)-2,2-dimethylcyclopropanecarboxylate],silafluofen [(4-ethoxyphenyl)(3-(4-fluoro-3-phenoxyphenyl)propyl)dimethylsilane]; thiadiazine derivatives such as buprofezin(2-t-butylimino-3-isopropyl-5-phenyl-1,3,5-thiadiazin-4-one);nitroimidazolidine derivatives; nereistoxin derivatives such as cartap(S,S′-(2-dimethylaminotrimethylene)bis(thiocarbamate), thiocyclam[N,N′-dimethyl-1,2,3-trithian-5-ylamine] and bensultap[S,S′-2-dimethylaminotrimethylene di(benzenethiosulfonate)];N-cyanoamidine derivatives such asN-cyano-N′-methyl-N′-(6-chloro-3-pyridylmethyl)acetamidine; chlorinatedhydrocarbons such as endosulfan[6,7,8,9,10,10-hexachloro-1,5,5a,6,9,9a-hexahydro-6,9-methano-2,4,3-benzodioxathiepineoxide], γ-BHC [1,2,3,4,5,6-hexachlorocyclohexane] and1,1-bis(chlorophenyl)-2,2,2-trichloroethanol; benzoylphenylureacompounds such as chlorfluazuron[1-(3,5-dichloro-4-(3-chloro-5-trifluoromethylpyridyn-2-yloxy)phenyl)-3-(2,6-difluorobenzoyl)urea],teflubenzuron[1-(3,5-dichloro-2,4-difluorophenyl)-3-(2,6-difluorobenzoyl)urea] andflufenoxuron[1-(4-(2-chloro-4-trifluoromethylphenoxy)-2-fluorophenyl)-3-(2,6-difluorobenzoyl)urea];formamidine derivatives such as amitraz[N,N′-[(methylimino)dimethylidine]di-2,4-xylidine] and chlordimeform[N′-(4-chloro-2-methylphenyl)-N,N-dimethylmethanimidamide]; thioureaderivatives such as diafenthiuron[N-(2,6-diisopropyl-4-phenoxyphenyl)-N′-t-butylcarbodiimide];phenylpyrazole compounds; tebufenozide[N-t-butyl-N′-(4-ethylbenzoyl)-3,5-dimethylbenzhydrazide];4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-trifluoromethylpyrrole-3-carbonitrile;bromopropylate [isopropyl 4,4′-dibromobenzilate]; tetradifon[4-chlorophenyl 2,4,5-trichlorophenyl sulfone]; quinomethionate[S,S-6-methylquinoxalin-2,3-diyl dithiocarbonate]; propargite[2-(4-t-butylphenoxy)cyclohexyl prop-2-yl sulfite]; fenbutatin oxide[bis[tris (2-methyl-2-phenylpropyl)tin]oxide]; hexythiazox [(4RS,5RS)-5-(4-chlorophenyl)-N-chlorohexyl-4-methyl-2-oxo-1,3-thiazolidin-3-carboxamide];clofentezine [3,6-bis(2-chlorophenyl)-1,2,4,5-tetrazine]; pyridathioben[2-t-butyl-5-(4-t-butylbenzylthio)-4-chloropyridazin-3(2H)-one];fenpyroximate [t-butyl(E)-4-[(1,3-dimethyl-5-phenoxypyrazol-4-yl)methyleneaminooxymethyl]benzoate];tebufenpyrad[N-(4-t-butylbenzyl)-4-chloro-3-ethyl-1-methyl-5-pyrazolecarboxamide];polynactins complex [tetranactin, dinactin and trinactin]; milbemectin;abamectin; ivermectin; azadirachtin [AZAD]; pyrimidifen[5-chloro-N-[2-{4-(2-ethoxyethyl)-2,3-dimethylphenoxy}ethyl]-6-ethylpyrimidin-4-amine]and pymetrozine[2,3,4,5-tetrahydro-3-oxo-4-[(pyridin-3-yl)methyleneamino]-6-methyl-1,2,4-triazine.

Examples of the plant diseases to be controlled by the present compoundinclude Pyricularia oryzae and Cochlioholus miyaheanus and Rhizoctoniasolani of rice; Erysiphe graminis, Gibberella zeae, Pucciniastriiformis, P. graminis, P. recondita, P. hordei, Typhula sp.,Micronectriella nivalis, Ustilago tritici, U. nuda, Tilletia caries,Pseudocercosporella herpotrichoides, Rhynchosporium secalis, Septoriatritici and Leptosphaeria nodorum, of wheat and barley; Diaporthe citri,Elsinoe fawcetti, Penicillium digitatum and P. italicum of citrus;Sclerotinia mali, Valsa mali, Podosphaera leucotricha, Alternaria maliand Venturia inaequalis of apple; Venturia nashicola, V. pirina,Alternaria kikuchiana and Gymnosporangium haraeanum of pear; Sclerotiniacinerea, Cladosporium carpophilum and Phomopsis sp. of peach; Elsinoeampelina, Glomerella cingulata, Uncinula necator, Phakopsoraampelopsidis, Guignardia bidwellii and Plasmopara viticola, of grape;Gloeosporium kaki, Cercospora kaki and Mycosphaerella nawae of Japanesepersimmon; Colletotrichum lagenarium, Sphaerotheca fuliginea,Mycosphaerella melonis, Fusarium oxysporum, Pseudoperonospora cubensisand Phytophthora sp. of gourd; Alternaria solani, Cladosporium fulvum,Phytophthora infestans and Pythium sp. of tomato; Phomopsis vexans andErysiphe cichoracearum, of eggplant; Alternaria japonica andCercosporella brassicae of Cruciferae vegetables; Puccinia allii ofleek; Cercospora kikuchii, Elsinoe glycines and Diaporthe phaseolorumvar. sojae of soybean; Colletotrichum lindemthianum of kidney bean;Cercospora personata and Cercospora arachidicola of peanut; Erysiphepisi of pea; Alternaria solani and Phytophthora infestans of potato;Sphaerotheca humuli of strawberry; Exobasidium reticulatum and Elsinoeleucospila of tea; Alternaria longipes, Erysiphe cichoracearum,Colletotrichum tabacum, Peronospora tabacina and Phytophthora nicotianaeof tobacco; Cercospora beticola of sugar beet; Diplocarpon rosae andSphaerotheca pannosa of rose; Septoria chrysanthemi-indici and Pucciniahoriana of chrysanthemum; and Botrytis cinerea and Sclerotiniasclerotiorum of various crops.

EXAMPLES

The present invention is explained by production examples, formulationexamples and test examples below and it is not restricted by thefollowing examples.

At first, the production examples of the present compounds and referenceproduction examples of the intermediates of the present compounds. Thenumbers of the present compounds are the compound numbers described inthe table below.

Production Example 1

Two hundred milligrams (200 mg) ofN-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-methylphenyl)acrylamide(0.586 mmol), 28 mg (0.70 mmol) of 60% sodium hydride, 2 ml of anhydrousN,N-dimethylformamide and 1 ml of anhydrous diethyl ether were mixed and0.5 ml of bromofluoromethane was added thereto at −5° C. The mixture wasstirred at −5° C. for 30 minutes and then stirred at 0° C. for 1 hour.The reaction mixture was added to water and extracted with ethylacetate. The organic layer was washed with 5% hydrochloric acid,saturated aqueous sodium bicarbonate solution and saturated brinesubsequently, dried over anhydrous magnesium sulfate and concentratedunder reduced pressure. The residue was subjected to silica gelpreparative thin layer chromatography (eluent, hexane:ethyl acetate=2:1)to give 205 mg ofN-[2-(3,4-dimethoxyphenyl)ethyl]-3-fluoromethoxy-2-(4-methylphenyl)acrylamide(the present compound 1-4).

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.1-7.2(5H,m), 6.7-6.8(3H,m), 6.5(1H,s),5.43(2H,d,J=53 Hz), 3.87(3H,s), 3.85(3H,s), 3.62(2H,m), 2.84(2H,t),2.34(3H,s).

By using N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(3-methylphenyl)acrylamide in place ofN-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-methylphenyl)acrylamide,N-[2-(3,4-dimethoxyphenyl)ethyl]-3-fluoromethoxy-2-(3-methylphenyl)acrylamide(the present compound 1034) was obtained according to production example1.

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.0-7.3(4H,m), 6.6-6.8(4H,m), 6.46(1H,br),5.44(2H,d,J=53.4 Hz), 3.86(3H,s), 3.85(3H,s), 3.6-3.7(2H,m),2.84(2H,t,J=6.9 Hz), 2.33(3H,s)

Production Example 2

Five hundred milligrams (500 mg) ofN-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-methylphenyl)acrylamide(1.46 mmol), 0.31 g (1.7 mmol) of 30% aqueous potassium hydroxidesolution, 0.1 g (0.3 mmol) of tetrabutylammonium bromide and 10 ml ofethylene glycol dimethyl ether were mixed and chlorodifluoromethane gaswas blown thereto at room temperature. After a small amount of 30%aqueous potassium hydroxide solution was further added, a sample wastaken out from the reaction mixture and the disappearance of thestarting material was confirmed by thin layer chromatograph analysis.Then, 5% hydrochrolic acid was added to the reaction mixture, which wasfollowed by extracted with ethyl acetate, washed with 5% hydrochrolicacid, saturated aqueous sodium bicarbonate solution and saturated brinesubsequently, dried over anhydrous magnesium sulfate and concentratedunder reduced pressure. The residue was washed with hexane to give 474mg of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-difluoromethoxy-2-(4-methylphenyl)acrylamide (the presentcompound 1005).

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.11-7.19(4H,m), 6.85(1H,s), 6.72-6.78(3H,m), 6.36(1H,t,J=71.8 Hz), 3.86(3H,s), 3.83(3H,s), 3.49(2H,m),2.83(2H,t), 2.34(3H,s)

Production Example 3

One gram (1.00 g) ofN-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-chlorophenyl) acrylamide(2.66 mmol), 130 mg (3.25 mmol) of 60% sodium hydride and 10 ml ofanhydrous N,N-dimethylformamide were mixed and 0.46 g ofbromofluoromethane was added thereto at −15° C. The mixture was stirredat −15° C. for 30 minutes and then stirred at 0° C. for 1 hour. Thereaction mixture was added to water and extracted with ethyl acetate.The organic layer was washed with 5% hydrochloric acid and saturatedbrine subsequently, dried over anhydrous magnesium sulfate andconcentrated under reduced pressure. The residue was subjected to silicagel preparative thin layer chromatography (eluent, hexane:ethylacetate=1:1) to give 100 mg ofN-[2-(3,4-dimethoxyphenyl)ethyl]-3-fluoromethoxy-2-(4-chlorophenyl)acrylamide(the present compound 1016).

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.0-7.3(4H,m), 6.5-6.8(5H,m), 5.41(2H,d,J=53.4 Hz), 3.84(3H,s), 3.83(3H,s), 3.5-3.7(2H,m), 2.82(2H,t,J=6.9 Hz)

Production Example 4

Five hundred milligrams (500 mg) ofN-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-chlorophenyl)acrylamide(1.33 mmol), 2.00 g (3.56 mmol) of 10% aqueous potassium hydroxidesolution, 87 mg (0.266 mmol) of tetrabutylammonium bromide and 10 ml ofethylene glycol dimethyl ether were mixed and chlorodifluoromethane gaswas blown thereto at room temperature. After a sample was taken out fromthe reaction mixture and the disappearance of the starting material wasconfirmed by thin layer chromatograph analysis, 5% hydrochloric acid wasadded to the reaction mixture. The reaction mixture was extracted withethyl acetate, washed with 5% hydrochloric acid, saturated aqueoussodium bicarbonate solution and saturated brine subsequently, dried overanhydrous magnesium sulfate and concentrated under reduced pressure. Theresidue was subjected to silica gel chromatography (eluent, hexane:ethylacetate=2:1) and the obtained residue was washed with hexane to give 360mg ofN-[2-(3,4-dimethoxyphenyl)ethyl]-3-difluoromethoxy-2-(4-chlorophenyl)acrylamide.

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.2-7.4(4H,m), 6.7-6.9(4H,m), 6.35(1H,t,J=71.4 Hz), 6.13(1H,br), 3.86(3H,s), 3.83(3H,s), 3.6-3.7(2H,m),2.84(2H,t, J=6.8 Hz).

Production Example 5

Five hundred miligrams (500 mg) ofN-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-methylphenyl)acrylamide(1.47 mmol), 0.11 g (1.47 mmol) of 3-chloropropyne and 5 ml of anhydrousN,N-dimethylformamide were mixed and 64 mg (1.61 mmol) of 60% sodiumhydride was added thereto at 0-5° C. The mixture was stirred at 0-10° C.for 30 minutes and then stirred at room temperature. Water was added tothe reaction mixture, followed by extracted with ethyl acetate, washedwith 5% hydrochrolic acid and saturated brine subsequently, dried overanhydrous magnesium sulfate and concentrated under reduced pressure. Theresidue was subjected to silica gel chromatography (eluent, hexane:ethylacetate=1:1) to give 180 mg ofN-[2-(3,4-dimethoxyphenyl)ethyl]-3-(2-propynyloxy)-2-(4-methylphenyl)acrylamide(the present compound 1182).

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.0-7.3(4H,m), 6.7-6.9(4H,m), 6.70(1H,s),4.51(2H,d,J=2.4 Hz), 3.86(6H,s), 3.5-3.7(2H,m), 2.83(2H,t,J=6.9 Hz),2.59(1H,t, J=2.4 Hz), 2.32(3H,s).

By using N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-chlorophenyl)acrylamide in place ofN-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-methylphenyl)acrylamide,N-[2-(3,4-dimethoxyphenyl)ethyl]-3-(2-propynyloxy)-2-(4-chlorophenyl)acrylamide(the present compound 1185) was obtained according to production example5.

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.60(1H,s), 7.2-7.4(4H,m), 7.0-7.1(2H,m),6.73(1H,d,J=7.9 Hz), 6.62(1H,d,J=1.9 Hz), 6.56(1H,dd,J=8.0,1.9 Hz),5.28(1H,br), 4.52(2H,d,J=2.3 Hz), 3.87(3H,s), 3.83(3H,s), 3.4-3.6(2H,m),2.71(2H,t,J=6.9 Hz)

Production Example 6

0.76 g (2.0 mmol) ofN-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamideand 8ml of anhydrous N,N-dimethylformamide were mixed and 0.5 ml ofbromofluoromethane was added thereto at −15° C. 88 mg (2.2 mmol) of 60%sodium hydride was added and stirred at −15° C. for 30 minutes and thenstirred at approximately 0° C. for 1.5 hours. Water was added to thereaction mixture, followed by extracted with ethyl acetate, washed with5% hydrochrolic acid and saturated brine subsequently, dried overanhydrous magnesium sulfate and concentrated under reduced pressure. Theresidue was subjected to silica gel preparative thin layerchromatography (eluent, hexane:ethyl acetate=1:1) to give 0.68 g ofN-[2-(3,4-dimethoxyphenyl)ethyl]-3-fluoromethoxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide(thepresent compound 1103).

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.00(3H,s), 6.7-6.9(4H,m), 6.42(1H,br),5.43(2H,d,J=53.7 Hz), 3.85(3H,s), 3.84(3H,s), 3.6-3.7(2H,m),2.83(2H,t,J=6.9 Hz), 2.7-2.8(4H,m), 1.7-1.9(4H,m).

Production Example 7

A mixture of 380 mg (0.920 mmol) ofN-[2-(3,4-dimethoxyphenyl)ethyl]-3-fluoromethoxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide,420 mg (1.01 mmol) of Lawesson's Reagent and 5 ml of anhydroustetrahydrofuran was refluxed by heating for 3 hours. Water and ethylacetate were added to the reaction mixture, and the ethyl acetate layerwas washed with aqueous sodium hydroxide solution, aqueous ammoniumchloride solution and saturated brine subsequently, dried over anhydrousmagnesium sulfate and concentrated under reduced pressure. The residuewas subjected to silica gel chromatography (eluent, hexane:ethylacetate=3:1) to give 222 mg ofN-[2-(3,4-dimethoxyphenyl)ethyl]-3-fluoromethoxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylthioamide(the present compound 1160).

¹H-NMR(CDCl₃, TMS) δ(ppm): 8.11(1H,s), 7.0-7.1(2H,m), 6.77(2H,d, J=6.0Hz), 6.70(1H,d,J=8.2 Hz), 6.60(1H,d,J=1.7 Hz), 6.55(1H,dd,J=7.9,1.9 Hz),5.48(2H,d,J=53.5 Hz), 3.9-4.0(2H,m), 3.85(3H,s), 3.81(3H,s),2.83(2H,t,J=6.7 Hz), 2.6-2.8(4H,m), 1.7-1.9(4H,m).

By using3-difluoromethoxy-N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-2-(4-methylphenyl)acrylamidein place ofN-[2-(3,4-dimethoxyphenyl)ethyl]-3-fluoromethoxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide,3-difluoromethoxy-N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-2-(4-methylphenyl)acrylthioamide(the present compound 1445) was obtained according to production example7.

¹H-NMR(CDCl₃, TMS) δ(ppm): 8.20(1H,s), 7.1-7.2(2H,m), 6.8-7.0(4H,m),6.38(1H,t, J=71.0 Hz), 6.5-6.6(1H,m), 4.74(2H,s), 3.9-4.0(2H,m),3.79(3H,s), 2.83(2H,t,J=6.8 Hz), 2.52(1H,t,J=2.1 Hz), 2.39(3H,s).

Production Example 8

Five hundred milligrams (500 mg) ofN-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide(1.31 mmol), 1.80 g (3.28 mmol) of 10% aqueous potassium hydroxidesolution, 87 mg (0.262 mmol) of tetrabutylammonium bromide and 10 ml ofethylene glycol dimethyl ether were mixed and chlorodifluoromethane gaswas blown thereto at room temperature. A sample was taken out from thereaction mixture and the disappearance of the starting material wasconfirmed by thin layer chromatograph analysis. Then, 5% hydrochrolicacid was added to the reaction mixture, which was followed by extractedwith ethyl acetate, washed with 5% hydrochrolic acid, saturated aqueoussodium bicarbonate solution and saturated brine subsequently, dried overanhydrous magnesium sulfate and concentrated under reduced pressure. Theresidue was subjected to silica gel chromatography (eluent, hexane:ethylacetate=2:1) and the obtained residue was washed with hexane to give 350mg of3-difluoromethoxy-N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide(the present compound 1104).

¹H-NMR(CDCl₃, TMS) δ(ppm): 6.9-7.1(3H,m), 6.7-6.9(4H,m), 6.36(1H,t,J=71.8 Hz), 6.01(1H,br), 3.86(3H,s), 3.83(3H,s), 3.6-3.7(2H,m),2.83(2H,t, J=6.9 Hz), 2.6-2.8(4H,m), 1.7-1.9(4H,m).

By usingN-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-methoxyphenyl)acrylamidein place ofN-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide,3-difluoromethoxy-N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(4-methoxyphenyl)acrylamide(the present compound 1023) was obtained according to production example8.

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.1-7.3(2H,m), 6.7-6.9(6H,m), 6.35(1H,t,J=71.7 Hz), 6.04(1H,br), 3.86(3H,s), 3.82(3H,s), 3.80(3H,s),3.6-3.7(2H,m), 2.83 (2H,t,J=6.8 Hz).

By usingN-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(naphthalen-2-yl)acrylamidein place ofN-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide,3-difluoromethoxy-N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(naphthalen-2-yl)acrylamide(the present compound 2077) was obtained according to production example8.

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.7-7.9(4H,m), 7.4-7.6(3H,m), 7.01(1H,s),6.7-6.8(3H,m), 6.41(1H,t,J=71.6 Hz), 6.08(1H,br), 3.84(3H,s),3.79(3H,s), 3.6-3.7(2H,m), 2.86(2H,t,J=6.9 Hz).

By using N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-bromophenyl)acrylamide in place ofN-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide,2-(4-bromophenyl)-3-difluoromethoxy-N-[2-(3,4-dimethoxyphenyl)ethyl]acrylamide(the present compound 1020) was obtained according to production example8.

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.4-7.5(2H,m), 7.1-7.2(2H,m), 6.89(1H,s),6.7-6.9(3H,m), 6.35(1H,t,J=71.4 Hz), 6.14(1H,br), 3.86(3H,s),3.83(3H,s), 3.6-3.7(2H,m), 2.84(2H,t,J=6.9 Hz).

By usingN-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-trifluoromethylphenyl)acrylamidein place of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide,3-difluoromethoxy-N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(4-trifluoromethylphenyl)acrylamide (the present compound 1029) was obtained according toproduction example 8.

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.4-7.6(4H,m), 6.95(1H,s), 6.7-6.9(3H,m),6.37(1H,t,J=71.5 Hz), 6.21(1H,br), 3.85(3H,s), 3.83(3H,s),3.6-3.7(2H,m), 2.85(2H,t,J=6.9 Hz).

By using N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(indan-5-yl)acrylamide in place ofN-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide,3-difluoromethoxy-N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(indan-5-yl)acrylamide(the present compound 1122) was obtained according to production example8.

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.0-7.2(3H,m), 6.6-6.9(4H,m), 6.35(1H,t, 71.7Hz), 6.02(1H,br), 3.85(3H,s), 3.83(3H,s), 3.6-3.7(2H,m), 2.8-3.0(6H,m),2.0-2.1(2H,m).

By using N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-nitrophenyl)acrylamide in place ofN-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide,3-difluoromethoxy-N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(4-nitrophenyl)acrylamide(the present compound 1247) was obtained according to production example8.

¹H-NMR(CDCl₃, TMS) δ(ppm): 8.1-8.2(2H,m), 7.4-7.5(2H,m), 7.03(1H,s),6.6-6.9(3H,m), 6.37(1H,t,J=70.8 Hz), 6.28(1H,br), 3.8-3.9(6H,m),3.6-3.7(2H,m), 2.86(2H,t,J=6.7 Hz).

By usingN-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-methylthiophenyl)acrylamidein place ofN-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide,3-difluoromethoxy-N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(4-methylthiophenyl)acrylamide(the present compound 1026) was obtained according to production example8.

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.20(4H,s), 6.7-6.9(4H,m), 6.36(1H,t, J=71.5Hz), 6.07(1H,br), 3.86(3H,s), 3.82(3H,s), 3.6-3.7(2H,m), 2.84(2H,t,J=6.9 Hz), 2.49(3H,s).

By usingN-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(3,4-dichlorophenyl)acrylamidein place ofN-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide,2-(3,4-dichlorophenyl)-3-difluoromethoxy-N-[2-(3,4-dimethoxyphenyl)ethyl]acrylamide(the present compound 1065) was obtained according to production example8.

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.3-7.5(2H,m), 7.14(1H,dd,J=8.5,2.1 Hz),6.90(1H,s), 6.7-6.9(3H,m), 6.35(1H,t,J=71.4 Hz), 6.21(1H,br),3.87(3H,s), 3.86(3H,s), 3.6-3.7(2H,m), 2.85(2H,t,J=6.8 Hz).

By usingN-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-isopropylphenyl)acrylamidein place ofN-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide,3-difluoromethoxy-N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(4-isopropylphenyl)acrylamide(the present compound 1251) was obtained according to production example8.

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.0-7.2(4H,m), 6.7-6.9(4H,m), 6.38(1H,t,J=71.7 Hz), 6.05(1H,br), 3.86(3H,s), 3.83(3H,s), 3.5-3.7(2H,m),2.8-3.0(3H,m), 1.23(6H,d, J=6.8 Hz).

By usingN-[3-(3,4-dimethoxyphenyl)propyl]-3-hydroxy-2-(4-methylphenyl)acrylamidein place ofN-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide,3-difluoromethoxy-N-[3-(3,4-dimethoxyphenyl)propyl]-2-(4-methylphenyl)acrylamide(the present compound 1476) was obtained according to production example8.

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.1-7.3(4H,m), 6.87(1H,s), 6.7-6.8(3H,m),6.46(1H,t,J=72.1 Hz), 5.98(1H,br), 3.86(3H,s), 3.85(3H,s),3.4-3.5(2H,m), 2.63(2H,t, J=7.43 Hz), 2.34(3H,s), 1.8-2.0(2H,m).

Production Example 9

Five hundred milligrams (500 mg) of3-difluoromethoxy-N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide(1.16 mmol) and 5 ml of anhydrous N,N-dimethylformamide were mixed andcooled, and then 49 mg (1.22 mmol) of 60% sodium hydride was addedthereto and stirred at 0° C. for 30 minutes. To the mixture, 164 mg(1.16 mmol) of methyl iodide was added and stirred at 0° C. for 30minutes and then at room temperature for 2 hours. Water was added to thereaction mixture, which which was followed by extracted with ethylacetate, washed with 5% hydrochrolic acid and saturated brinesubsequently, dried over anhydrous magnesium sulfate and concentratedunder reduced pressure. The residue was subjected to silica gelpreparative thin layer chromatography (eluent, hexane:ethyl acetate=3:1)to give 460 mg of3-difluoromethoxy-N-[2-(3,4-dimethoxyphenyl)ethyl]-N-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide(the present compound 1125).

¹H-NMR(CDCl₃, TMS) δ(ppm): 6.5-7.1(7H,m), 6.38(1H,t,J=72.4 Hz), 3.85(3H,s), 3.82(3H,s), 3.7-3.8(2H,m), 2.8-3.0(5H,m), 2.6-2.8(4H,m),1.7-1.9(4H,m).

Production Example 10

Six hundred milligrams (600 mg) ofN-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide(1.57 mmol), 0.14 g (1.89 mmol) of 3-chloropropyne, 280 mg (2.05 mmol)of potassium carbonate and 10 ml of anhydrous N,N-dimethylformamide weremixed and stirred at room temperature. Water was added to the reactionmixture, which was followed by extracted with ethyl acetate, washed with5% hydrochrolic acid and saturated brine subsequently, dried overanhydrous magnesium sulfate and concentrated under reduced pressure. Theresidue was subjected to silica gel chromatography (eluent, hexane:ethylacetate=1:1) to give 415 mg ofN-[2-(3,4-dimethoxyphenyl)ethyl]-3-(2-propynyloxy)-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide(the present compound 1196).

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.00(3H,s), 6.7-6.9(4H,m), 6.69(1H,s),4.50(2H,d,J=2.4 Hz), 3.86(6H,s), 3.5-3.7(2H,m), 2.7-2.9(6H,m),2.61(1H,t, J=2.4 Hz), 1.7-1.9(4H,m).

By using 1,1,3-trichloropropene in place of 3-chloropropyne,3-(3,3-dichloroallyloxy)-N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide(the present compound 1232) was obtained according to production example10.

¹H-NMR(CDCl₃, TMS) δ(ppm): 6.9-7.0(3H,m), 6.7-6.9(4H,m), 6.53(1H,s),5.98(1H,d,J=6.4 Hz), 4.51(2H,d,J=6.5 Hz), 3.86(3H,s), 3.85(3H,s),3.6-3.7(2H,m), 2.7-2.9(6H,m), 1.7-1.9(4H,m).

By using 1-chloro-2-fluoroethane in place of 3-chloropropyne,N-[2-(3,4-dimethoxyphenyl)ethyl]-3-(2-fluoroethoxy)-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide(the present compound 1241) was obtained according to production example10.

¹H-NMR(CDCl₃, TMS) δ(ppm): 6.99(3H,s), 6.93(1H,br), 6.7-6.9(3H,m),6.60(1H,s), 4.4-4.7(2H,m), 4.0-4.2(2H,m), 3.86(6H,s), 3.6-3.7(2H,m),2.7-2.9(6H,m), 1.7-1.9(4H,m).

Production Example 11

Three hundred milligrams (300 mg) ofN-[2-(3,4-dimethoxyphenyl)ethyl]-3-(2-propynyloxy)-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide(0.716 mmol), 20 mg (0.0766 mmol) of tetrabutylammonium fluoride, 100 mg(0.716 mmol) of potassium carbonate and 2 ml of carbon tetrachloridewere mixed and stirred at room temperature. Water was added to thereaction mixture, which was followed by extracted with ethyl acetate,washed with 5% hydrochrolic acid and saturated brine subsequently, driedover anhydrous magnesium sulfate and concentrated under reducedpressure. The residue was subjected to silica gel chromatography(eluent, hexane:ethyl acetate=1:1) to give 140 mg of3-(3-chloro-2-propynyloxy)-N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide(the present compound 1223).

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.00(3H,s), 6.7-6.9(4H,m), 6.65(1H,s),4.50(2H,d,J=2.6 Hz), 3.86(6H,s), 3.5-3.7(2H,m), 2.7-2.9(6H,m),1.7-1.9(4H,m).

Production Example 12

239 mg of3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide(0.572 mmol), 128 mg (1.72 mmol) of 3-chloropropyne, 3 ml of anhydrousN,N-dimethylformamide and 20 mg (0.50 mmol) of 60% sodium hydride weremixed and stirred at room temperature for 4 hours. Water was added tothe reaction mixture, which was followed by extracted with ethylacetate, washed with 5% hydrochrolic acid, saturated aqueous sodiumbicarbonate solution and saturated brine subsequently, dried overanhydrous magnesium sulfate and concentrated under reduced pressure. Theresidue was subjected to silica gel column chromatography to give 225 mgof3-difluoromethoxy-N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide(the present compound 1268).

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.00(3H,s), 6.7-6.9(4H,m), 6.69(1H,s),4.50(2H,d, J=2.4 Hz), 3.86(6H,s), 3.5-3.7(2H,m), 2.7-2.9(6H,m),2.61(1H,t, J=2.4 Hz), 1.7-1.9(4H,m).

By using bromoethane in place of 3-chloropropyne,3-difluoromethoxy-N-[2-(4-ethoxy-3-methoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1143) was obtained according toproduction example 12.

¹H-NMR(CDCl₃, TMS) δ(ppm): 6.99(3H,s), 6.7-6.9(4H,m), 6.37(1H,t,J=71.8Hz), 6.12(1H,br), 4.06(2H,q,J=8.1 Hz), 3.80(3H,s), 3.5-3.7(2H,m),2.6-2.9(6H,m), 1.7-1.9(4H,m), 1.44(3H,t,J=7.0 Hz).

By using chloropropane in place of 3-chloropropyne,3-difluoromethoxy-N-[2-(3-methoxy-4-propoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1258) was obtained according toproduction example 12.

¹H-NMR(CDCl₃, TMS) δ(ppm): 6.9-7.1(3H,m), 6.4-6.9(4H,m), 6.36(1H,t,J=71.9 Hz), 6.05(1H,br), 3.97(2H,t,J=6.8 Hz), 3.82(3H,s), 3.5-3.7(2H,m),2.6-2.9(6H,m), 1.7-1.9(6H,m), 1.03(3H,t,J=7.4 Hz).

By using chloroacetonitrile in place of 3-chloropropyne,N-[2-(4-cyanomethoxy-3-methoxyphenyl)ethyl]-3-difluoromethoxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide(the present compound 1274) was obtained according to production example12.

¹H-NMR(CDCl₃, TMS) δ(ppm): 6.9-7.1(4H,m), 6.7-6.9(3H,m), 6.39(1H,t,J=71.8 Hz), 6.10(1H,br), 4.79(2H,s), 3.83(3H,s), 3.6-3.7(2H,m),2.6-2.9(6H,m), 1.7-1.9(4H,m).

By using allyl chloride in place of 3-chloropropyne,N-[2-(4-allyloxy-3-methoxyphenyl)ethyl]-3-difluoromethoxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide(the present compound 1266) was obtained according to production example12.

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.00(3H,s), 6.6-6.9(4H,m), 6.35(1H,t, J=71.9Hz), 5.9-6.2(2H,m), 5.2-5.5(2H,m), 4.58(2H,dd,J=3.9,1.3 Hz), 3.83(3H,s),3.5-3.7(2H,m), 2.6-2.9(6H,m), 1.7-1.9(4H,m).

By using 1-chloro-2-butyne in place of 3-chloropropyne,N-[2-{4-(2-butynyloxy)-3-methoxyphenyl}ethyl]-3-difluoromethoxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide(the present compound 1269) was obtained according to production example12.

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.00(3H,s), 6.9-7.0(1H,m), 6.84(1H,s),6.7-6.8(2H,m), 6.34(1H,t,J=71.7 Hz), 6.03(1H,br), 4.69(2H,q,J=2.3 Hz),3.82(3H,s), 3.6-3.7(2H,m), 2.83(2H,t,J=6.9 Hz), 2.7-2.8(4H,m),1.83(3H,t,J=2.2 Hz), 1.7-1.8(4H,m).

By using methoxymethyl chloride in place of 3-chloropropyne,3-difluoromethoxy-N-[2-(3-methoxy-4-methoxymethoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide(the present compound 1284) was obtained according to production example12.

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.0-7.1(4H,m), 6.85(1H,s), 6.7-6.8(2H,m),6.34(1H,t,J=71.6 Hz), 6.02(1H,br), 5.20(2H,s), 3.83(3H,s),3.6-3.7(2H,m), 3.51(3H,s), 2.7-2.9(6H,m), 1.7-1.9(4H,m)

By using isopropyl chloride in place of 3-chloropropyne,3-difluoromethoxy-N-[2-(4-isopropoxy-3-methoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1259) was obtained according toproduction example 12.

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.00(3H,s), 6.6-6.9(4H,m), 6.35(1H,t, J=71.7Hz), 6.02(1H,br), 4.4-4.6(1H,m), 3.80(3H,s), 3.6-3.7(2H,m),2.7-2.9(6H,m), 1.7-1.9(4H,m), 1.35(6H,d,J=6.1 Hz).

Production Example 13

Eighty milligrams (80 mg) of acetyl chloride (1.00 mmol) were added to amixture of 420 mg (1.00 mmol), of3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide, 120 mg (1.20 mmol) of triethylamine and 5 ml oftetrahydrofuran at 0° C. and stirred at 0° C. for 30 minutes and then atroom temperature for 2 hours. Water and ethyl acetate were added to thereaction mixture. The organic layer was washed with 5% hydrochrolic acidand saturated brine subsequently, dried over anhydrous magnesium sulfateand concentrated under reduced pressure. The residue was subjected tosilica gel chromatography (eluent, hexane:ethyl acetate=3:1) to give 260mg of3-difluoromethoxy-N-[2-(3-methoxy-4-acetyloxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide(the present compound 1282).

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.01(3H,s), 6.7-7.0(4H,m), 6.34(1H,t, J=71.2Hz), 6.18(1H,br), 3.77(3H,s), 3.6-3.7(2H,m), 2.83(2H,t,J=6.7 Hz),2.7-2.8 (4H,m), 2.30(3H,s), 1.7-1.8(4H,m).

Production Example 14

One and a half grams (1.5 g) ofN-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-methylphenyl)acrylamide(4.39 mmol), 193 mg (4.83 mmol) of 60% sodium hydride, 10 ml ofanhydrous dimethoxyethane and 10 ml of anhydrous diethyl ether weremixed, 0.8 ml of dibromodifluoromethane was added thereto at 0° C. andstirred at 0° C. for 3 hours. Water was added to the reaction mixture,which was followed by extracted with ethyl acetate, washed with water,dried over anhydrous magnesium sulfate and concentrated under reducedpressure. The residue was subjected to silica gel column chromatography(eluent, hexane:ethyl acetate=2:1) to give 1.0 g ofN-[2-(3,4-dimethoxyphenyl)ethyl]-3-bromodifluoromethoxy-2-(4-methylphenyl)acrylamide(the present compound 1197).

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.1-7.2(4H,m), 6.7-6.8(4H,m), 6.4(1H,s),3.86(3H,s), 3.83(3H,s), 3.66(2H,m), 2.84(2H,t), 2.35(3H,s).

Production Example 15

Five hundred hundred milligrams (500 mg) of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-bromodifluoromethoxy-2-(4-methylphenyl)acrylamide (1.06 mmol),0.5 ml of hydrogen fluoride-pyridine complex, 340 mg (1.57 mmol) ofmercury oxide and 1 ml of isopropyl ether were mixed and stirred at roomtemperature for 2 hours. Aqueous sodium bicarbonate solution and celitewere added to the reaction mixture and filtered. Water was added to thefiltrate, which was followed by extracted with ethyl acetate, washedwith 5% hydrochrolic acid, saturated aqueous sodium bicarbonate solutionand saturated brine subsequently, dried over anhydrous magnesium sulfateand concentrated under reduced pressure. The residue was recrystallizedfrom t-butyl methyl ether and hexane to give 0.35 g ofN-[2-(3,4-dimethoxyphenyl)ethyl]-3-trifluoromethoxy-2-(4-methylphenyl)acrylamide (the present compound 1006).

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.1-7.2(4H,m), 6.7-6.8(3H,m), 6.71(1H,s),6.1(1H,s), 3.84(3H,s), 3.82(3H,s), 3.62(2H,m), 2.89(2H,t), 2.32(3H,s).

Production Example 16

4.20 g (9.19 mmol) ofN-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide,14.3 g (23.0 mmol) of 10% aqueous potassium hydroxide solution, 0.60 g(1.84 mmol) of tetrabutylammonium bromide and 40 ml of ethylene glycoldimethyl ether were mixed and chlorodifluoromethane gas was blownthereto at room temperature. After a sample was taken out from thereaction mixture and the disappearance of the starting material wasconfirmed by thin layer chromatography, 5% hydrochloric acid was addedto the reaction mixture. The reaction mixture was extracted with ethylacetate, washed with 5% hydrochloric acid, saturated aqueous sodiumbicarbonate solution and saturated brine subsequently, dried overanhydrous magnesium sulfate and concentrated under reduced pressure. Theresidue was subjected to silica gel chromatography (eluent, hexane:ethylacetate=2:1) and the obtained product was washed with hexane to give 2.4g ofN-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-difluoromethoxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide(the present compound 1281).

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.2-7.5(5H,m), 6.9-7.1(3H,m), 6.6-6.9(4H,m),6.26(1H,t,J=71.6 Hz), 6.02(1H,br), 5.13(2H,s), 3.84(3H,s),3.5-3.7(2H,m), 2.7-2.9(6H,m), 1.7-1.9(4H,m).

By usingN-[2-(2,3-dihydrobenzo[1,4]dioxin-6-yl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamidein place ofN-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide,3-difluoromethoxy-N-[2-(2,3-dihydrobenzo[1,4]dioxin-6-yl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide(the present compound 1450) was obtained according to production example16.

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.01(3H,s), 6.85(1H,s), 6.6-6.8(3H,m),6.41(1t,J=71.6 Hz), 6.02(1H,br), 4.24(4H,s), 3.5-3.7(2H,m),2.7-2.8(6H,m), 1.7-1.9(4H,m).

By usingN-[2-(3-chloro-4-methoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamidein place ofN-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide,N-[2-(3-chloro-4-methoxyphenyl)ethyl]-3-difluoromethoxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide(the present compound 1447) was obtained according to production example16.

¹H-NMR(CDCl₃, TMS) δ(ppm): 6.9-7.2(4H,m), 6.8-6.9(3H,m), 6.40(1H,t,J=71.6 Hz), 6.00(1H,br), 3.88(3H,s), 3.5-3.6(2H,m), 2.7-2.9(6H,m),1.7-1.9(4H,m).

By usingN-[2-(4-methoxy-3-methylphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamidein place ofN-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide,3-difluoromethoxy-N-[2-(4-methoxy-3-methylphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide(the present compound 1448) was obtained according to production example16.

¹H-NMR(CDCl₃, TMS) δ(ppm): 6.9-7.0(4H,m), 6.7-6.9(3H,m), 6.34(1H,t,J=71.7 Hz), 6.00(1H,br), 3.81(3H,s), 3.5-3.7(2H,m), 2.7-2.8(6H,m),2.17(3H,s), 1.7-1.9(4H,m).

Production Example 17

2.40 g (4.73 mmol) ofN-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-difluoromethoxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide,1.20 g (7.09 mmol) of 48% hydrobromic acid and 30 ml of acetic acid weremixed and stirred at 80° C. for 2 hours. Water was added to to thereaction mixture, which was followed by extracted with ethyl acetate,washed with 5% hydrochrolic acid and saturated brine subsequently, driedover anhydrous magnesium sulfate and concentrated under reducedpressure. The residue was subjected to silica gel column chromatography(eluent, hexane:ethyl acetate=1:1) to give 1.81 g of3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide(the present compound 1371).

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.0-7.1(3H,m), 6.84(1H,d,J=3.3 Hz),6.80(1H,s), 6.6-6.7(2H,m), 6.36(1H,t,J=71.8 Hz), 6.12(1H,br),5.78(1H,s), 3.82(3H,s), 3.5-3.7(2H,m), 2.4-2.8(6H,m), 1.7-1.9(4H,m).

Production Example 18

417 mg (1.00 mmol) of3-difluoromethoxy-N-[2-(3-hydroxy-4-methoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide,5 ml of anhydrous N,N-dimethylformamide, 74 mg (1.00 mmol) of3-chloropropyne and 50 mg (1.25 mmol) of 60% sodium hydride were mixedand stirred at room temperature for 3 hours. Water was added to to thereaction mixture, which was followed by extracted with ethyl acetate,washed with 5% hydrochrolic acid, saturated aqueous sodium bicarbonatesolution and saturated brine subsequently, dried over anhydrousmagnesium sulfate and concentrated under reduced pressure. The residuewas subjected to silica gel column chromatography to give 162 mg of3-difluoromethoxy-N-[2-{4-methoxy-3-(2-propynyloxy)phenyl}ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide(the present compound 1299).

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.00(3H,s), 6.8-6.9(4H,m), 6.37(1H,t, J=71.7Hz), 6.03(1H,br), 4.71(2H,d,J=2.4 Hz), 3.85(3H,s), 3.6-3.7(2H,m),2.83(2H, t,J=6.8 Hz), 2.7-2.8(4H,m), 2.47(1H,t,J=2.4 Hz), 1.7-1.9(4H,m).

By using bromoethane in place of 3-chloropropyne,3-difluoromethoxy-N-[2-(3-ethoxy-4-methoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide(the present compound 1320) was obtained according to production example18.

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.00(3H,s), 6.7-6.9(4H,m), 6.36(1H,t, J=71.7Hz), 6.02(1H,br), 4.04(2H,q,J=7.0 Hz), 3.84(3H,s), 3.5-3.7(2H,m),2.7-2.9 (6H,m), 1.7-1.9(4H,m), 1.44(3H,t,J=7.0 Hz).

By using chloroacetonitrile in place of 3-chloropropyne,N-[2-(3-cyanomethoxy-4-methoxyphenyl)ethyl]-3-difluoromethoxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide(the present compound 1305) was obtained according to production example18.

¹H-NMR(CDCl₃, TMS) δ(ppm): 6.8-7.1(7H,m), 6.40(1H,t,J=72.1 Hz),6.05(1H,br), 4.77(2H,s), 3.86(3H,s), 3.5-3.7(2H,m), 2.84(2H,t,J=6.9 Hz),2.7-2.8(4H,m), 1.7-1.9(4H,m).

Production Example 19

Five hundred milligrams (500 mg) of3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(4-methylphenyl)acrylamide(1.33 mmol), 5 ml of anhydrous N,N-dimethylformamide, 196 mg (2.65 mmol)of 3-chloropropyne and 60 mg (1.46 mmol) of 60% sodium hydride werestirred at room temperature for 2 hours. Water was added to to thereaction mixture, which was followed by extracted with ethyl acetate,washed with 5% hydrochrolic acid, saturated aqueous sodium bicarbonatesolution and saturated brine subsequently, dried over anhydrousmagnesium sulfate and concentrated under reduced pressure. The residuewas subjected to silica gel column chromatography (eluent, hexane:ethylacetate=2:1) to give 242 mg of3-difluoromethoxy-N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-2-(4-methylphenyl)acrylamide(the present compound 1353).

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.1-7.2(4H,m), 6.95(1H,d,J=8.25 Hz),6.85(1H,s), 6.7-6.8(2H,m), 6.35(1H,t,J=71.7 Hz), 6.11(1H,br),4.73(2H,d,J=2.3 Hz), 3.81(3H,s), 3.6-3.7(2H,m), 2.83(2H,t,J=6.9 Hz),2.49(1H,d,J=2.4 Hz), 2.32(3H,s).

By using3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(indan-5-yl)acrylamidein place of3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(4-methylphenyl)acrylamide,3-difluoromethoxy-2-(indan-5-yl)-N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]acrylamide(the present compound 1360) was obtained according to production example19.

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.1-7.0(2H,m), 6.9-7.1(2H,m), 6.85(1H,s),6.7-6.8(2H,m), 6.35(1H,t,J=71.6 Hz), 6.06(1H,br), 4.74(2H,d,J=2.4 Hz),3.83(3H,s), 3.6-3.7(2H,m), 2.8-2.9(6H,m), 2.49(1H,t,J=2.4 Hz),2.0-2.2(2H,m).

By using3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(4-methoxyphenyl)acrylamidein place of3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(4-methylphenyl)acrylamide,3-difluoromethoxy-2-(4-methoxyphenyl)-N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]acrylamide(the present compound 1358) was obtained according to production example19.

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.2-7.3(2H,m), 6.7-7.0(6H,m),6.34(1H,t,J=71.6 Hz), 6.05(1H,br), 4.74(2H,d,J=2.5 Hz), 3.83(3H,s),3.81(3H,s), 3.6-3.7(2H,m), 2.84(2H,t,J=6.8 Hz), 2.49(1H,t,J=2.5 Hz).

By using3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-phenylacrylamidein place of3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(4-methylphenyl)acrylamide,3-difluoromethoxy-N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-2-phenylacrylamide(the present compound 1388) was obtained according to production example19.

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.3-7.4(5H,m), 6.96(1H,d,J=8.7 Hz),6.90(1H,s), 6.7-6.8(2H,m), 6.36(1H,t,J=71.5 Hz), 6.07(1H,br),4.75(2H,d,J=2.4 Hz), 3.83(3H,s), 3.6-3.7(2H,m), 2.85(2H,t,J=6.8 Hz),2.50(1H,t,J=2.4 Hz).

By using3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(4-trifluoromethylphenyl)acrylamidein place of3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(4-methylphenyl)acrylamide,3-difluoromethoxy-N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-2-(4-trifluoromethylphenyl)acrylamide(the present compound 1357) was obtained according to production example19.

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.59(2H,d,J=8.2 Hz), 7.43(2H,d,J=8.0 Hz),6.9-7.0(2H,m), 6.7-6.8(2H,m), 6.35(1H,t,J=71.0 Hz), 6.21(1H,br),4.75(2H,d, J=2.2 Hz), 3.84(3H,s), 3.6-3.7(2H,m), 2.87(2H,t,J=6.8 Hz),2.49(1H,t,J=2.2 Hz).

By using3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(4-ethylphenyl)acrylamidein place of3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(4-methylphenyl)acrylamide,3-difluoromethoxy-2-(4-ethylphenyl)-N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]acrylamide(the present compound 1354) was obtained according to production example19.

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.1-7.3(4H,m), 6.96(1H,d,J=8.7 Hz), 6.87(1H,s), 6.7-6.8(2H,m), 6.35(1H,t,J=71.6 Hz), 6.06(1H,br),4.75(2H,d,J=2.4 Hz), 3.83(3H,s), 3.6-3.7(2H,m), 2.85(2H,t,J=6.8 Hz),2.64(2H,q,J=6.8 Hz), 2.50(1H,t, J=2.4 Hz).

By using3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(4-fluorophenyl)acrylamidein place of3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(4-methylphenyl)acrylamide,3-difluoromethoxy-2-(4-fluorophenyl)-N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]acrylamide(the present compound 1392) was obtained according to production example19.

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.2-7.3(2H,m), 6.9-7.1(3H,m), 6.87(1H,s),6.7-6.8(2H,m), 6.34(1H,t,J=71.3 Hz), 6.17(1H,br), 4.76(2H,d,J=2.4 Hz),3.85(3H,s), 3.6-3.7(2H,m), 2.85(2H,t,J=6.8 Hz), 2.64(2H,q,J=6.8 Hz),2.50(1H,t,J=2.4 Hz).

By using3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(naphthalen-2-yl)acrylamidein place of3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(4-methylphenyl)acrylamide,3-difluoromethoxy-N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-2-(naphthalen-2-yl)acrylamide(the present compound 2202) was obtained according to production example19.

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.7-7.9(4H,m), 7.4-7.5(3H,m), 7.02(1H,s),6.93(1H,d,J=8.6 Hz), 6.7-6.8(2H,m), 6.39(1H,t,J=71.5 Hz), 6.11(1H,br),4.72(2H,d, J=2.2 Hz), 3.78(3H,s), 3.6-3.7(2H,m), 2.87(2H,t,J=6.8 Hz),2.48(1H,t,J=2.5 Hz).

By using3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(5-methylthiophen-2-yl)acrylamidein place of3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(4-methylphenyl)acrylamide,3-difluoromethoxy-2-(5-methylthiophen-2-yl)-N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]acrylamide (the present compound 2133) was obtainedaccording to production example 19.

¹H-NMR(CDCl₃, TMS) δppm): 7.62(1H,s), 6.95(1H,d,J=8.6 Hz), 6.15-6.72(3H,m), 6.4(1H,br), 4.74(2H,d,J=2.4 Hz), 3.83(3H,s), 3.6(2H,m),2.79(2H,t, J=6.9 Hz), 2.50(1H,t,J=2.4 Hz), 2.47(3H,s).

By using3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(3,4-dichlorophenyl)acrylamidein place of3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(4-methylphenyl)acrylamide,3-difluoromethoxy-2-(3,4-dichlorophenyl)-N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]acrylamide(the present compound 1429) was obtained according to production example19.

¹H-NMR(CDCl₃, TMS) δppm): 7.4-7.5(2H,m), 7.13(1H,dd,J=2.14, 8.2 Hz),6.97(1H,d,J=7.1 Hz), 6.92(1H,s), 6.7-6.8 (2H,m), 6.0-6.7(2H,m),4.75(2H,d,J=2.4 Hz), 3.84(3H,s), 3.6(2H,m), 2.85(2H,t, J=6.5 Hz),2.51(1H,t,J=2.4 Hz).

By using3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)-1-methylethyl]-2-(4-methylphenyl)acrylamidein place of3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(4-methylphenyl)acrylamide,3-difluoromethoxy-N-[2-(3-methoxy-4-(2-propynyloxy)phenyl)-1-methylethyl]-2-(4-methylphenyl)acrylamide(the present compound 1465) was obtained according to production example19.

¹H-NMR(CDCl₃, TMS) δppm): 7.1-7.2(4H,m), 6.95(1H,d,J=7.9 Hz),6.85(1H,s), 6.7-6.8(2H,m), 6.36(1H,t,J=71.7 Hz), 5.78(1H,d,J=7.8 Hz),4.75(2H,d,J=2.2 Hz), 4.3-4.5(1H,m), 3.82(3H,s), 2.7-2.9(2H,m),2.49(1H,t, J=2.1 Hz), 2.34(3H,s), 1.20(3H,d,J=6.7 Hz).

By using bromomethylcyclopropane in place of 3-chloropropyne,N-[2-(4-cyclopropylmethoxy-3-methoxyphenyl)ethyl]-3-difluoromethoxy-2-(4-methylphenyl)acrylamide(the present compound 1271) was obtained according to production example19.

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.1-7.2(4H,m), 6.7-6.9(4H,m), 6.35(1H,t,J=71.7 Hz), 6.01(1H,br), 3.8-3.9(5H,m), 3.6-3.7(2H,m), 2.82(2H,t, J=6.8Hz), 2.33(3H,s), 1.2-1.4(1H,m), 0.6-0.7(2H,m), 0.3-0.4(2H,m).

Production Example 20

477 mg (1.20 mmol) of3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(4-chlorophenyl)acrylamide,5 ml of anhydrous N,N-dimethylformamide, 180 mg (2.40 mmol) of3-chloropropyne and 72 mg (1.80 mmol) of 60% sodium hydride were stirredat room temperature for 2 hours. Water was added to to the reactionmixture, which was followed by extracted with ethyl acetate, washed with5% hydrochrolic acid, saturated aqueous sodium bicarbonate solution andsaturated brine subsequently, dried over anhydrous magnesium sulfate andconcentrated under reduced pressure. The residue was subjected to silicagel column chromatography (eluent, hexane:ethyl acetate=2:1) to give 70mg of3-difluoromethoxy-N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-2-(4-chlorophenyl)acrylamide(the present compound 1355).

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.1-7.4(4H,m), 6.97(1H,d,J=8.7 Hz), 6.89(1H,s), 6.7-6.8(2H,m), 6.34(1H,t,J=71.3 Hz), 6.17(1H,br),4.75(2H,d,J=2.4 Hz), 3.84(3H,s), 3.6-3.7(2H,m), 2.85(2H,t,J=7.0 Hz),2.50(1H,d,J=2.4 Hz).

Production Example 21

Two hundred milligrams (200 mg) of3-hydroxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(4-methylphenyl)acrylamide(0.611 mmol), 2 ml of anhydrous N,N-dimethylformamide, 144 mg (1.22mmol) of 3-bromopropyne and 173 mg (1.25 mmol) of potassium carbonatewere stirred at room temperature for 2 hours and then at 50° C. for 4hours. Water was added to to the reaction mixture, which was followed byextracted with ethyl acetate, washed with 5% hydrochrolic acid,saturated aqueous sodium bicarbonate and saturated brine subsequently,dried over anhydrous magnesium sulfate and concentrated under reducedpressure. The residue was subjected to silica gel column chromatography(eluent, hexane:ethyl acetate=1:1) to give 100 mg ofN-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-3-(2-propynyloxy)-2-(4-methylphenyl)acrylamide (thepresent compound 1364).

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.1-7.2(4H,m), 6.98(1H,d,J=8.6 Hz),6.6-6.9(4H,m), 4.74(2H,d,J=2.5 Hz), 4.49(2H,d,J=2.5 Hz), 3.85(3H,s),3.6-3.7 (2H,m), 2.83(2H,t,J=6.9 Hz), 2.59(1H,d,J=2.3 Hz),2.50(1H,d,J=2.2 Hz), 2.32(3H,s).

Production Example 22

Three hundred milligrams (300 mg) of3-hydroxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(4-chlorophenyl)acrylamide(0.863 mmol) and 3 ml of anhydrous N,N-dimethylformamide were mixed and320 mg (4.32 mmol) of 3-chloropropyne was added thereto at 0-5° C., andthen 100 mg (2.59 mmol) of 60% sodium hydride was added at 0-5° C. Themixture was stirred for 1 hour at 0-5° C. and further at roomtemperature. Water was added to to the reaction mixture, which wasfollowed by extracted with ethyl acetate, washed with 5% hydrochrolicacid and saturated brine subsequently, dried over anhydrous magnesiumsulfate and concentrated under reduced pressure. The residue wassubjected to silica gel chromatography (eluent, hexane:ethylacetate=2:1) to give 160 mg of2-(4-chlorophenyl)-N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-3-(2-propynyloxy)acrylamide (the present compound 1367).

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.2-7.3(4H,m), 6.9-7.0(2H,m), 6.7-6.8 (3H,m),4.75(2H,d,J=2.4 Hz), 4.52(2H,d,J=2.4 Hz), 3.86(3H,s), 3.6-3.7(2H,m),2.84(2H,t,J=6.9 Hz), 2.63(1H,d,J=2.4 Hz), 2.51(1H,d,J=2.42 Hz).

Production Example 23

4.17 g (10.00 mmol) ofN-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-hydroxy-2-(4-methylphenyl)acrylamide,22.4 g (40.0 mmol) of 10% aqueous potassium hydroxide solution, 1.62 g(5.00 mmol) of tetrabutylammonium bromide and 50 ml of ethylene glycoldimethyl ether were mixed and chlorodifluoromethane gas was blownthereto at room temperature. After a sample was taken out from thereaction mixture and the disappearance of the starting material wasconfirmed by thin layer chromatography, 5% hydrochloric acid was addedto the reaction mixture, which was followed by extracted with ethylacetate, washed with 5% hydrochrolic acid, saturated aqueous sodiumbicarbonate solution and saturated brine subsequently, dried overanhydrous magnesium sulfate and concentrated under reduced pressure. Theresidue was washed with diethyl ether to give 3.46 g ofN-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-difluoromethoxy-2-(4-methylphenyl)acrylamide(the present compound 1451).

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.2-7.5(5H,m), 7.1-7.2(4H,m), 6.84(1H,s),6.80(1H,d,J=8.2 Hz), 6.74(1H,d,J=1.6 Hz), 6.65(1H,dd,J=8.0,1.8 Hz),6.26(1H,t, J=71.6 Hz), 6.02(1H,br), 5.13(2H,s), 3.84(3H,s),3.6-3.7(2H,m), 2.81(2H,t, J=6.8 Hz), 2.33(3H,s).

Production Example 24

9.40 g ofN-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-difluoromethoxy-2-(4-methylphenyl)acrylamide(20.1 mmol), 3.72 g (22.1 mmol) of 48% hydrobromic acid and 95 ml ofacetic acid were mixed and stirred at 80° C. for 1.5 hours. The solventwas distilled off from the reaction mixture under reduced pressure andthe residue was subjected to silica gel column chromatography (eluent,hexane:ethyl acetate=2:1) to give 4.55 g of3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(4-methylphenyl)acrylamide(the present compound 1452).

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.1-7.2(4H,m), 6.8-6.9(2H,m), 6.6-6.7(2H,m,),6.35(1H,t,J=71.7 Hz), 6.02(1H,br), 5.51(1H,s), 3.84(3H,s),3.6-3.7(2H,m), 2.81(2H,t, J=6.9 Hz), 2.34(3H,s).

Production Example 25

1.48 g (3.38 mmol) ofN-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-hydroxy-2-(4-chlorophenyl)acrylamide,4.3 g (8.46 mmol) of 10% aqueous potassium hydroxide solution, 220 mg(0.677 mmol) of tetrabutylammonium bromide and 15 ml of ethylene glycoldimethyl ether were mixed and chlorodifluoromethane gas was blownthereto at room temperature. After a sample was taken out from thereaction mixture and the disappearance of the starting material wasconfirmed by thin layer chromatography, 5% hydrochloric acid was addedto the reaction mixture, which was followed by extracted with ethylacetate, washed with 5% hydrochrolic acid, saturated aqueous sodiumbicarbonate solution and saturated brine subsequently, dried overanhydrous magnesium sulfate and concentrated under reduced pressure. Theresidue was washed with hexane to give 1.45 g ofN-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-2-(4-chlorophenyl)-3-difluoromethoxyacrylamide(the present compound 1453).

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.2-7.5(9H,m), 6.87(1H,s), 6.80(1H,d, J=8.3Hz), 6.75(1H,d,J=2.0Hz), 6.66(1H,dd,J=8.0,2.0Hz), 6.23(1H,t,J=71.7 Hz),6.12(1H,br), 5.14(2H,s), 3.85(3H,s), 3.6-3.7(2H,m), 2.82(2H,t,J=6.8 Hz)

Production Example 26

1.45 g (2.97 mmol) ofN-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-2-(4-chlorophenyl)-3-difluoromethoxyacrylamide,751 mg (4.46 mmol) of 48% hydrobromic acid and 15 ml of acetic acid weremixed and stirred at 80° C. for 1.5 hours. Water was added to to thereaction mixture, which was followed by extracted with ethyl acetatetwice, washed with saturated brine twice, dried over anhydrous magnesiumsulfate and concentrated under reduced pressure. The residue wassubjected to silica gel column chromatography (eluent, hexane:ethylacetate=1:1) to give 880 mg of2-(4-chlorophenyl)-3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]acrylamide(the present compound 1454).

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.2-7.4(4H,m), 6.88(1H,s), 6.84(1H,d, J=7.8Hz), 6.6-6.8(2H,m), 6.34(1H,t,J=71.4 Hz), 6.14(1H,br), 5.53(1H,s), 3.85(3H,s), 3.6-3.7(2H,m), 2.82(2H,t,J=6.8 Hz).

Reference Production Example 1

A mixture of 5.00 g (33.3 mmol) of (4-methylphenyl)acetic acid, 5.94 g(49.9 mmol) of thionyl chloride, 0.12 g (1.6 mmol) ofN,N-dimethylformamide and 20 ml of toluene was stirred at 100° C. for 1hour, cooled and concentrated under reduced pressure. The residue wasadded to a mixture of 6.34 g (35.0 mmol)2-(3,4-dimethoxyphenyl)ethylamine, 8.6 g (67 mmol) ofdiisopropylethylamine and 25 ml of toluene at 0° C. and kept at 0° C.for 30 minutes and at room temperature for 6 hours. Water and ethylacetate were added to the reaction mixture and precipitated solid wascollected with filtration. The obtained solid was dried to give 5.76 gof N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(4-methylphenyl)acetamide.

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.0-7.2(4H,m), 6.72(1H,d,J=8.2 Hz),6.57-6.60(2H, m), 5.4(1H,s), 3.86(3H,s), 3.82(3H,s), 3.49(2H,s),3.43(2H,m), 2.67(2H,t,J=6.9 Hz), 2.34(3H,s).

One gram (1.0 g) of N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(4-methylphenyl)acetamide (3.2 mmol), 1.68 g (9.64 mmol) oft-butoxybis(dimethylamino)methane and 15 ml of N,N-dimethylformamidewere mixed and stirred at 90° C. for 3 hours and then at 110° C. for 3hours. Water was added to the reaction mixture, which was followed byextracted with ethyl acetate, washed with saturated brine twice, driedover anhydrous magnesium sulfate and the solvent was distilled off underreduced pressure to give 1.20 g of crudeN-[2-(3,4-dimethoxyphenyl)ethyl]-3-dimethylamino-2-(4-methylphenyl)acrylamide.

One gram (1.0 g) of crudeN-[2-(3,4-dimethoxyphenyl)ethyl]-3-dimethylamino-2-(4-methylphenyl)acrylamide(2.7 mmol), 12 ml of 5% hydrochloric acid and 20 ml of tetrahydrofuranwere mixed and stirred at room temperature for 2 hours. Water was addedto the reaction mixture, which was followed by extracted with ethylacetate twice, washed with saturated brine twice, dried over anhydrousmagnesium sulfate and the solvent was distilled off under reducedpressure. The residue was washed with hexane and dried to give 0.76 g ofN-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-methylphenyl)acrylamide.

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.26(1H,s), 7.0-7.1(4H,m), 6.6-6.7(3H,m),5.5(1H,s), 3.86(3H,s), 3.82(3H,s), 3.51(2H,m), 2.75(2H,t,J=6.9 Hz),2.35(3H,s).

Reference Production Example 2

A mixture of 5.00 g (29.3 mmol) of (4-chlorophenyl)acetic acid, 5.23 g(43.9 mmol) of thionyl chloride and 50 ml of toluene was stirred at 50°C. for 30 minutes and then 80° C. for 2.5 hours, cooled and concentratedunder reduced pressure. The residue was added to a mixture of 5.18 g(28.5 mmol) 2-(3,4-dimethoxyphenyl)ethylamine, 3.46 g (34.2 mmol) oftriethylamine and 50 ml tetrahydrofuran at 0° C. and kept at 0° C. for30 minutes and at room temperature for 3 hours. Water and ethyl acetatewere added to the reaction mixture and precipitated solid was collectedwith filtration. The obtained solid was dried to give 5.75 g ofN-[2-(3,4-dimethoxyphenyl)ethyl]-2-(4-chlorophenyl) acetamide.

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.2-7.3(2H,m), 7.0-7.1(2H,m), 6.72(1H,d,J=8.1 Hz), 6.61(1H,d,J=2.0 Hz), 6.51(1H,dd,J=8.0,1.9 Hz), 5.31(1H,br),3.87(3H,s), 3.83(3H,s), 3.4-3.5(4H,m), 2.68(2H,t,J=6.8 Hz).

5.75 g (17.2 mmol) ofN-[2-(3,4-dimethoxyphenyl)ethyl]-2-(4-chlorophenyl) acetamide, 9.00 g(51.6 mmol) of t-butoxybis(dimethylamino)methane and 90 ml ofN,N-dimethylformamide were mixed and stirred at 90° C. for 3 hours andthen at 110° C. for 3 hours. Water was added to the reaction mixture,which was followed by extracted with ethyl acetate, washed withsaturated brine twice, dried over anhydrous magnesium sulfate and thesolvent was distilled off under reduced pressure to give 6.68 g of crudeN-[2-(3,4-dimethoxyphenyl)ethyl]-3-dimethylamino-2-(4-chlorophenyl)acrylamide.

6.60 g (17.2 mmol) of crudeN-[2-(3,4-dimethoxyphenyl)ethyl]-3-dimethylamino-2-(4-chlorophenyl)acrylamide,80 ml of 5% hydrochloric acid and 100 ml of tetrahydrofuran were mixedand stirred at room temperature for 2 hours. Water was added to thereaction mixture, which was followed by extracted with ethyl acetatetwice, washed with saturated brine twice, dried over anhydrous magnesiumsulfate and the solvent was distilled off under reduced pressure. Theresidue was washed with hexane and dried to give 4.46 g ofN-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-chlorophenyl)acrylamide.

¹H-NMR(CDCl₃, TMS) δ(ppm): 13.66(1H,d,J=11.34 Hz), 7.2-7.3(2H,m),7.0-7.1(3H,m), 6.74(1H,d,J=8.1 Hz), 6.5-6.6(2H,m), 5.32(1H,br),3.87(3H,s), 3.80(3H,s), 3.5-3.6(2H,m), 2.75(2H,d,J=6.8 Hz).

Reference Production Example 3

According to the description of JP hei10-87602A,(5,6,7,8-tetrahydronaphthalen-2-yl)acetic acid was obtained.

A mixture of 3.60 g (18.9 mmol) of(5,6,7,8-tetrahydronaphthalen-2-yl)acetic acid, 3.38 g (28.4 mmol) ofthionyl chloride and 40 ml of toluene was stirred at 50° C. for 30minutes and then 80° C. for 2.5 hours, cooled and concentrated underreduced pressure. The residue was added to a mixture of 3.43 g (18.9mmol) 2-(3,4-dimethoxyphenyl)ethylamine, 2.30 g (22.7 mmol) oftriethylamine and 40 ml of tetrahydrofuran at 0° C. and kept at 0° C.for 30 minutes and at room temperature for 3 hours. Water and ethylacetate were added to the reaction mixture and precipitated solid wascollected with filtration. The obtained solid was dried to give 5.78 gofN-[2-(3,4-dimethoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acetamide.

¹H-NMR(CDCl₃, TMS) δ(ppm): 6.99(1H,d,J=8.1 Hz), 6.8-6.9(2H,m),6.5-6.8(3H,m), 5.42(1H,br), 3.85(3H,s), 3.82(3H,s), 3.4-3.5(4H,m),2.6-2.8(6H,m), 1.7-1.9(4H,m).

2.65 g (7.50 mmol) ofN-[2-(3,4-dimethoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acetamide,3.92 g (22.5 mmol) of t-butoxybis (dimethylamino)methane and 30 ml ofN,N-dimethylformamide were mixed and stirred at 90° C. for 3 hours andthen at 110° C. for 3 hours. Water was added to the reaction mixture,which was followed by extracted with ethyl acetate, washed withsaturated brine twice, dried over anhydrous magnesium sulfate and thesolvent was distilled off under reduced pressure to give 3.30 g of crudeN-[2-(3,4-dimethoxyphenyl)ethyl]-3-dimethylamino-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide.

Three grams (3.00 g) of crudeN-[2-(3,4-dimethoxyphenyl)ethyl]-3-dimethylamino-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide(7.35 mmol), 30 ml of 5% hydrochloric acid and 30 ml of tetrahydrofuranwere mixed and stirred at room temperature for 1.5 hours. Water wasadded to the reaction mixture, which was followed by extracted withethyl acetate twice, washed with saturated brine twice, dried overanhydrous magnesium sulfate and the solvent was distilled off underreduced pressure. The residue was washed with hexane and dried to give2.20 g ofN-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide.

¹H-NMR(CDCl₃, TMS) δ(ppm): 13.61(1H,d,J=11.2 Hz), 6.9-7.1(2H,m),6.6-6.8(5H, m), 5.56(1H,br), 3.86(3H,s), 3.82(3H,s), 3.4-3.6(2H,m),2.6-2.9(6H,m), 1.7-1.9(4H,m).

Reference Production Example 4

15.2 g (0.1 mol) of vanilline, 20.5 g (0.12 mol) of benzyl bromide, 17.9g (0.13 mol) of potassium carbonate and 150 ml of N,N-dimethylformamidewere mixed and stirred at 50° C. for 2 hours. Water was added to thereaction mixture, which was followed by extracted with ethyl acetate,washed with 5% hydrochloric acid and then saturated brine, dried overanhydrous magnesium sulfate and the solvent was distilled off underreduced pressure. The residue was washed with hexane and dried to give23.1 g of 4-benzyloxy-3-methoxybenzaldehyde.

¹H-NMR(CDCl₃, TMS) δ(ppm): 9.83(1H,s), 7.5-7.3(7H,m), 6.98(1H,d, J=8.2Hz), 5.24(2H,s), 3.95(3H,s).

23.1 g (95.7 mmol) of 4-benzyloxy-3-methoxybenzaldehyde, 8.76 g (143mmol) of nitromethane and 250 ml of acetic acid were mixed and 7.07 g(96.7 mmol) of butylamine was added dropwise thereto. The mixture wasrefluxed for 2 hours by heating, and then cooled and poured intoice-water. The precipitated crystals were dissolved with ethyl acetate,washed with saturated brine, dried over anhydrous magnesium sulfate andthe solvent was distilled off under reduced pressure. The residue waswashed with hexane and dried to give 17.0 g of1-benzyloxy-2-methoxy-4-(2-nitrovinyl)benzene.

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.95(1H,d,J=13.5 Hz), 7.51(1H,d,J=14.7 Hz),7.3-7.5(5H,m), 5.24(2H,s), 3.95(3H,s).

6.78 g (178.8 mmol) of lithium aluminum hydride and 200 ml of anhydroustetrahydrofuran were mixed and an anhydrous tetrahydrofuran solution of17.0 g (59.6 mmol) of 1-benzyloxy-2-methoxy-4-(2-nitrovinyl)benzene wasadded dropwise thereto over about 90 minutes under vigorous stirring.The mixture was refluxed for 2 hours by heating, and then cooled andaqueous sodium hydroxide solution was added to the mixture. Theprecipitates were filtered off with celite-precoated glass filter andthe solvent was distilled off from the filtrate under reduced pressure.The residue was extracted with ethyl acetate, washed with saturatedbrine, dried over potassium carbonate and the solvent was distilled offunder reduced pressure to give 13.67 g of crude2-(3-methoxy-4-benzyloxyphenyl)ethylamine.

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.2-7.5(5H,m), 6.6-6.9(3H,m), 5.10(2H,s),3.85(3H,s), 2.90(2H,t,J=6.7 Hz), 2.66(2H,t,J=6.8 Hz), 2.0-2.4(2H,br).

8.01 g (31.2 mmol) of crude 2-(3-methoxy-4-benzyloxyphenyl)ethylamine,3.78 g (37.4 mmol) of triethylamine and 80 ml of tetrahydrofuran weremixed and cooled to 0° C. and then(5,6,7,8-tetrahydronaphthalen-2-yl)acetyl chloride was added dropwisethereto. The mixture was stirred at 0° C. for 30 minutes and further atroom temperature for 2 hours. Water was added to the reaction mixture,which was followed by extracted with ethyl acetate, washed with 5%hydrochloric acid and then saturated brine, dried over anhydrousmagnesium sulfate and the solvent was distilled off under reducedpressure. The residue was subjected to silica gel column chromatography(eluent, hexane:ethyl acetate=1:1) to give 8.3 g ofN-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acetamide.

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.1-7.2(4H,m), 6.72(1H,d,J=8.2 Hz),6.5-6.6(2H,m), 5.4(1H,s), 3.86(3H,s), 3.82(3H,s), 3.49(2H,s),3.3-3.4(2H,m), 2.67(2H,t,J=6.9 Hz), 2.34(3H,s).

8.8 g (13.6 mmol) ofN-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acetamide,8.9 g (51.1 mmol) of t-butoxybis (dimethylamino)methane and 100 ml ofN,N-dimethylformamide were mixed and stirred at 100° C. for 6 hours.Water was added to the reaction mixture, which was followed by extractedwith ethyl acetate, washed with saturated brine twice, dried overanhydrous magnesium sulfate and the solvent was distilled off underreduced pressure. To the residue, 50 ml of 5% hydrochloric acid and 100ml of tetrahydrofuran were added and stirred at room temperature for 2hours. Water was added to the reaction mixture, which was followed byextracted with ethyl acetate twice, washed with saturated brine twice,dried over anhydrous magnesium sulfate and the solvent was distilled offunder reduced pressure. The residue was subjected to silica gelchromatography (eluent, hexane:ethyl acetate=2:1) and dried to give 4.20g ofN-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide.

¹H-NMR(CDCl₃, TMS) δ(ppm): 13.61(1H,d,J=11.3 Hz), 7.2-7.5(5H,m),7.04(1H,d, J=11.0 Hz), 6.97(1H,d,J=8.2 Hz), 6.7-6.9(3H,m),6.66(1H,d,J=2.0 Hz), 6.59(1H,dd,J=8.3, 1.9 Hz), 5.55(1H,br), 5.11(2H,s),3.83(3H,s), 3.4-3.6(2H,m), 2.6-2.9(6H,m), 1.7-1.9(4H,m).

Reference Production Example 5

15.26 g (59.3 mmol) of crude 2-(3-methoxy-4-benzyloxyphenyl)ethylamine,9.09 g (89.0 mmol) of triethylamine and 100 ml of tetrahydrofuran weremixed and cooled to about 0° C. and then 5.44 g (32.28 mmol) of(4-methylphenyl)acetyl chloride was added dropwise thereto. The mixturewas stirred at 0° C. for 30 minutes and further at room temperature for3 hours. Water was added to the reaction mixture, which was followed byextracted with ethyl acetate, washed with 5% hydrochloric acid andsaturated brine subsequently, dried over anhydrous magnesium sulfate andthe solvent was distilled off under reduced pressure. The residue waswashed with hexane and dried to give 19.48 g ofN-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-2-(4-methylphenyl)acetamide.

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.2-7.5(5H,m), 7.0-7.1(4H,m), 6.73(1H,d,J=8.2 Hz), 6.62(1H,d,J=1.9 Hz), 6.46(1H,dd,J=8.1,1.9 Hz), 5.34(1H,br),5.12(2H,s), 3.83(3H,s), 3.4-3.5(4H,m), 2.64(2H,t,J=6.9 Hz), 2.32(3H,s).

11.68 g (30.0 mmol) ofN-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-2-(4-methylphenyl)acetamide and15.67 g (90.0 mmol) of t-butoxybis(dimethylamino) methane were mixed andstirred at 80° C. for 2 hours. The reaction mixture was cooled andtetrahydrofuran was added thereto. The reaction mixture was acidifiedwith 5% hydrochloric acid and stirred at room temperature for 2 hours.After the solvent was distilled off under reduced pressure, water and 5%hydrochloric acid were added to the residue, which was followed byextracted with chloroform twice, washed with saturated brine twice,dried over anhydrous magnesium sulfate and the solvent was distilled offunder reduced pressure. The residue was washed with hexane and dried togive 11.30 g ofN-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-hydroxy-2-(4-methylphenyl)acrylamide.

¹H-NMR(CDCl₃, TMS) δ(ppm): 13.61(1H,d,J=11.3 Hz), 7.2-7.5(5H,m),6.9-7.1(5H,m), 6.77(1H,d,J=8.1 Hz), 6.64(1H,d,J=1.6 Hz),6.56(1H,dd,J=8.1,1.6 Hz), 5.46(1H,br), 5.13(2H,s), 3.83(3H,s),3.4-3.6(2H,m), 2.73(2H,t,J=6.8 Hz), 2.33(3H,s).

Reference Production Example 6

2.14 g (11.97 mmol) of crude 2-(3-methoxy-4-benzyloxyphenyl)ethylamine,1.45 g (14.36 mmol) of triethylamine and 20 ml of tetrahydrofuran weremixed and cooled to about 0° C. and then 2.26 g (11.97 mmol) of(4-chlorophenyl)acetyl chloride was added dropwise thereto. The mixturewas stirred at 0° C. for 30 minutes and further at room temperature for2 hours. Water was added to the reaction mixture, which was followed byextracted with ethyl acetate, washed with 5% hydrochloric acid andsaturated brine subsequently, dried over anhydrous magnesium sulfate andthe solvent was distilled off under reduced pressure. The residue waswashed with hexane and dried to give 3.70 g ofN-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-2-(4-chlorophenyl)acetamide.

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.2-7.5(7H,m), 7.0-7.1(2H,m), 6.73(1H,d,J=8.3 Hz), 6.63(1H,d,J=2.0Hz), 6.43(1H,dd,J=8.0,2.0Hz), 5.29(1H,br),5.14(2H,s), 3.84(3H,s), 3.4-3.5(4H,m), 2.66(2H,t,J=6.8 Hz).

2.25 g (5.49 mmol) ofN-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-2-(4-chlorophenyl)acetamide and2.39 g (13.73 mmol) of t-butoxybis(dimethylamino) methane were mixed andstirred at 90° C. for 1.5 hours. The reaction mixture was cooled andtetrahydrofuran was added thereto. The reaction mixture was acidifiedwith 5% hydrochloric acid and stirred at room temperature for 2 hours.After the solvent was distilled off under reduced pressure, water and 5%hydrochloric acid were added to the residue, which was followed byextracted with ethyl acetate, washed with saturated brine twice, driedover anhydrous magnesium sulfate and the solvent was distilled off underreduced pressure. The residue was subjected to silica gel columnchromatography (eluent, hexane:ethyl acetate=2:1) to give 1.50 g ofN-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-hydroxy-2-(4-chlorophenyl)acrylamide.

¹H-NMR(CDCl₃, TMS) δ(ppm): 13.67(1H,d,J=11.0 Hz), 7.2-7.5(7H,m),6.9-7.1(3H,m), 6.76(1H,d,J=8.3 Hz), 6.65(1H,d,J=1.8 Hz),6.52(1H,dd,J=8.0,2.0 Hz), 5.32(1H,br), 5.15(2H,s), 3.84(3H,s),3.4-3.6(2H,m), 2.73(2H,t,J=6.8 Hz).

Reference Production Example 7

Two grams (2.00 g) ofN-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-hydroxy-2-(4-methylphenyl)acrylamide(4.79 mmol), 1.21 g (7.19 mmol) of 48% hydrobromic acid and 20 ml ofacetic acid were mixed and stirred at 80° C. for 1.5 hours. The solventwas distilled off from the reaction mixture under reduced pressure andthe residue was subjected to silica gel column chromatography (eluent,hexane:ethyl acetate=2:1) to give 630 mg of3-hydroxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(4-methylphenyl)acrylamide.

¹H-NMR(CDCl₃, TMS) δ(ppm): 13.6(1H,d,J=11.3 Hz), 6.9-7.2(5H,m),6.80(1H,d), J=7.8 Hz), 6.5-6.6(2H,m), 5.4-5.5(2H,m), 3.83(3H,s),3.4-3.6(2H,m), 2.74(2H,t,J=6.9 Hz), 2.35(3H,s).

Reference Production Example 8

1.60 g (3.66 mmol) ofN-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-hydroxy-2-(4-chlorophenyl)acrylamide,925 mg (5.49 mmol) of 48% hydrobromic acid and 15 ml of acetic acid weremixed and stirred at 80° C. for 1.5 hours. Water was added to thereaction mixture, which was followed by extracted with ethyl acetatetwice, washed with saturated brine twice, dried over anhydrous magnesiumsulfate and the solvent was distilled off under reduced pressure. Theresidue was subjected to silica gel column chromatography (eluent,hexane:ethyl acetate=2:1) to give 600 mg of2-(4-chlorophenyl)-3-hydroxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]acrylamide.

¹H-NMR(CDCl₃, TMS) δ(ppm): 13.6(1H,d,J=11.3 Hz), 7.2-7.4(2H,m),7.0-7.1(3H, m), 6.82(1H,d,J=6.7,1.7 Hz), 6.5-6.6(2H,m), 5.54(1H,s),5.32(1H,br), 3.83(3H,s), 3.4-3.6 (2H,m), 2.74(2H,t,J=6.9 Hz).

Reference Production Example 9

4.02 g (55.0 mmol) of butylamine was added dropwise to a mixture of 12.1g (50.0 mmol) of 4-benzyloxy-3-methoxybenzaldehyde, 5.63 g (75.0 mmol)of nitroethane and 120 ml of acetic acid and refluxed for 5 hours byheating. The reaction mixture was cooled and extracted with ethylacetate, washed with saturated brine, dried over anhydrous magnesiumsulfate and the solvent was distilled off under reduced pressure. Theresidue was subjected to silica gel column chromatography (eluent,hexane:ethyl acetate=4:1) to give 2.70 g of1-benzyloxy-2-methoxy-4-(2-nitropropenyl)benzene.

¹H-NMR(CDCl₃, TMS) δ(ppm): 8.04(1H,s), 7.3-7.5(5H,m), 6.9-7.1(3H,m),5.21(2H,s), 3.92(3H,s), 2.47(3H,s).

To a mixture of 1.03 g (27.1 mmol) of lithium aluminum hydride and 20 mlof anhydrous tetrahydrofuran, an anhydrous tetrahydrofuran solution of2.70 g (9.03 mmol) of 1-benzyloxy-2-methoxy-4-(2-nitropropenyl)benzenewas added dropwise under vigorous stirring over about 90 minutes andrefluxed for 2 hours by heating. The reaction mixture was cooled andaqueous sodium hydroxide solution was added thereto. After theprecipitates were filtered off with celite-precoated glass filter, thesolvent was distilled off from the filtrate under reduced pressure. Theresidue was extracted with ethyl acetate, washed with saturated brine,dried over potassium carbonate and the solvent was distilled off underreduced pressure to give 2.30 g of crude2-(4-benzyloxy-3-methoxyphenyl)-1-methylethylamine.

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.2-7.5(5H,m), 6.6-6.9(3H,m), 5.12(2H,s),3.87(3H,s), 3.1-3.2(1H,m), 2.4-2.8(2H,m), 1.4-2.0(2H,br),1.11(3H,d,J=6.3 Hz).

2.30 g (8.48 mmol) of crude2-(4-benzyloxy-3-methoxyphenyl)-1-methylethylamine, 1.03 g (10.2 mmol)of triethylamine and 25 ml of tetrahydrofuran were mixed and cooled toabout 0° C. and then 1.42 g (8.48 mmol) of (4-methylphenyl)acetylchloride was added dropwise thereto. The mixture was stirred at 0° C.for 30 minutes and further at room temperature for 2 hours. Water wasadded to the reaction mixture, which was followed by extracted withethyl acetate, washed with 5% hydrochloric acid and saturated brinesubsequently, dried over anhydrous magnesium sulfate and the solvent wasdistilled off under reduced pressure. The residue was washed with hexaneand dried to give 2.40 g ofN-[2-(4-benzyloxy-3-methoxyphenyl)-1-methylethyl]-2-(4-methylphenyl)acetamide.

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.3-7.5(5H,m), 6.9-7.1(4H,m), 6.72(1H,d,J=8.1Hz), 6.62(1H,d,J=1.9 Hz), 6.42(1H,dd,J=2.0,8.1 Hz), 5.1-5.3(2H,m),4.1-4.3(1H,m), 3.83(3H,s), 3.45(2H,s), 2.59(2H,d,J=6.4 Hz), 2.33(3H,s),1.04(3H,d,J=6.6 Hz).

2.40 g (5.95 mmol) ofN-[2-(4-benzyloxy-3-methoxyphenyl)-1-methylethyl]-2-(4-methylphenyl)acetamideand 3.10 g (17.8 mmol) of t-butoxybis(dimethylamino) methane were mixedand stirred at 80° C. for 2 hours. The reaction mixture was cooled andtetrahydrofuran was added thereto. The reaction mixture was acidifiedwith hydrochloric acid and stirred at room temperature for 2 hours.After the solvent was distilled off under reduced pressure, the residuewas extracted with chloroform washed with saturated brine twice, driedover anhydrous magnesium sulfate and the solvent was distilled off underreduced pressure. The residue was subjected to silica gel chromatography(eluent, hexane:ethyl acetate=3:2) and dried to give 1.90 g ofN-[2-(4-benzyloxy-3-methoxyphenyl)-1-methylethyl]-3-hydroxy-2-(4-methylphenyl)acrylamide.

¹H-NMR(CDCl₃, TMS) δ(ppm): 13.65(1H,d,J=11.2 Hz), 7.2-7.5(5H,m),6.9-7.2(5H, m), 6.76(1H,d,J=8.2 Hz), 6.63(1H,d,J=1.88 Hz),6.52(1H,dd,J=8.1,1.9Hz), 5.28(2H,d, J=7.6 Hz), 5.14(2H,s),4.2-4.4(1H,d), 3.83(3H,s), 3.6-3.8(2H,m), 2.35(3H,s), 1.11(3H,d, J=6.5Hz).

1.90 g (4.41 mmol) ofN-[2-(4-benzyloxy-3-methoxyphenyl)-1-methylethyl]-3-hydroxy-2-(4-methylphenyl)acrylamide,0.99 g (17.6 mmol) of 10% aqueous potassium hydroxide solution, 716 mg(2.20 mmol) of tetrabutylammonium bromide and 20 ml of ethylene glycoldimethyl ether were mixed and chlorodifluoromethane gas was blownthereto at room temperature to 50° C. After a sample was taken out fromthe reaction mixture and the disappearance of the starting material wasconfirmed by thin layer chromatograph analysis, the reaction mixture wascooled. Then, 5% hydrochrolic acid was added to the reaction mixture,which was followed by extracted with ethyl acetate, washed with 5%hydrochrolic acid, saturated brine subsequently, dried over anhydrousmagnesium sulfate and concentrated under reduced pressure. The residuewas washed with hexane to give 1.80 g ofN-[2-(4-benzyloxy-3-methoxyphenyl)-1-methylethyl]-3-difluoromethoxy-2-(4-methylphenyl)acrylamide.

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.2-7.5(5H,m), 7.0-7.2(4H,m), 6.7-6.9(4H,m),6.63 (1H,dd,J=8.0,1.8 Hz), 6.30(1H,t,J=71.7 Hz), 5.79(1H,d,J=8.1 Hz),5.13(2H,s), 4.3-4.6(1H,m), 3.83(3H,s), 2.6-2.9(2H,m), 2.33(3H,s),1.18(3H,d,J=6.6 Hz).

1.80 g (3.74 mmol) ofN-[2-(4-benzyloxy-3-methoxyphenyl)-1-methylethyl]-3-difluoromethoxy-2-(4-methylphenyl)acrylamide,693 mg (4.11 mmol) of 48% hydrobromic acid and 20 ml of acetic acid weremixed and stirred at 80° C. for 2 hours. The solvent was distilled offfrom the reaction mixture under reduced pressure and the residue wassubjected to silica gel column chromatography (eluent, hexane:ethylacetate=2:1) to give 1.10 g of3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)-1-methylethyl]-2-(4-methylphenyl)acrylamide.

¹H-NMR(CDCl₃, TMS) δ(ppm): 7.1-7.2(4H,m), 6.6-6.9(4H,m), 6.37(1H,t,J=71.5 Hz), 5.79(1H,d,J=7.7 Hz), 5.58(1H,s), 4.3-4.5(1H,m), 3.82(3H,s),2.6-2.9(2H,m), 2.34(3H,s), 1.18(3H,d,J=6.5 Hz).

Examples of the present compounds are given with their compound numbersbelow.

Compound given by formula [I]:

Nos. R¹X Ar Y R² A Z¹ Z² 1001 CH₂FO C₆H₅ O H CH₂CH₂ CH₃O CH₃O 1002 CHF₂OC₆H₅ O H CH₂CH₂ CH₃O CH₃O 1003 CF₃O C₆H₅ O H CH₂CH₂ CH₃O CH₃O 1004 CH₂FO4-CH₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1005 CHF₂O 4-CH₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O1006 CF₃O 4-CH₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1007 CH₂FO 4-C₂H₅C₆H₄ O HCH₂CH₂ CH₃O CH₃O 1008 CHF₂O 4-C₂H₅C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1009 CF₃O4-C₂H₅C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1010 CH₂FO 4-CH₃CH₂CH₂C₆H₄ O H CH₂CH₂CH₃O CH₃O 1011 CHF₂O 4-CH₃CH₂CH₂C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1012 CF₃O4-CH₃CH₂CH₂C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1013 CH₂FO 4-FC₆H₄ O H CH₂CH₂ CH₃OCH₃O 1014 CHF₂O 4-FC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1015 CF₃O 4-FC₆H₄ O HCH₂CH₂ CH₃O CH₃O 1016 CH₂FO 4-ClC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1017 CHF₂O4-ClC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1018 CF₃O 4-ClC₆H₄ O H CH₂CH₂ CH₃O CH₃O1019 CH₂FO 4-BrC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1020 CHF₂O 4-BrC₆H₄ O H CH₂CH₂CH₃O CH₃O 1021 CF₃O 4-BrC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1022 CH₂FO 4-CH₃OC₆H₄O H CH₂CH₂ CH₃O CH₃O 1023 CHF₂O 4-CH₃OC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1024CF₃O 4-CH₃OC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1025 CH₂FO 4-CH₃SC₆H₄ O H CH₂CH₂CH₃O CH₃O 1026 CHF₂O 4-CH₃SC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1027 CF₃O4-CH₃SC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1028 CH₂FO 4-CF₃C₆H₄ O H CH₂CH₂ CH₃OCH₃O 1029 CHF₂O 4-CF₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1030 CF₃O 4-CF₃C₆H₄ O HCH₂CH₂ CH₃O CH₃O 1031 CH₂FO 4-(CH₃)₃CC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1032CHF₂O 4-(CH₃)₃CC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1033 CF₃O 4-(CH₃)₃CC₆H₄ O HCH₂CH₂ CH₃O CH₃O 1034 CH₂FO 3-CH₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1035 CHF₂O3-CH₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1036 CF₃O 3-CH₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O1037 CH₂FO 3-C₂H₅C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1038 CHF₂O 3-C₂H₅C₆H₄ O HCH₂CH₂ CH₃O CH₃O 1039 CF₃O 3-C₂H₅C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1040 CH₂FO3-CH₃CH₂CH₂C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1041 CHF₂O 3-CH₃CH₂CH₂C₆H₄ O HCH₂CH₂ CH₃O CH₃O 1042 CF₃O 3-CH₃CH₂CH₂C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1043CH₂FO 3-FC₆H₄ O H CH₂CH₂ CH₃O CH3Q 1044 CHF₂O 3-FC₆H₄ O H CH₂CH₂ CH₃OCH₃O 1045 CF₃O 3-FC₆H₄ O H CH₂CH₂ CH3Q CH₃O 1046 CH₂FO 3-ClC₆H₄ O HCH₂CH₂ CH₃O CH₃O 1047 CHF₂O 3-ClC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1048 CF₃O3-ClC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1049 CH₂FO 3-BrC₆H₄ O H CH₂CH₂ CH₃O CH₃O1050 CHF₂O 3-BrC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1051 CF₃O 3-BrC₆H₄ O H CH₂CH₂CH₃O CH₃O 1052 CH₂FO 3-CH₃OC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1053 CHF₂O3-CH₃OC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1054 CF₃O 3-CH₃OC₆H₄ O H CH₂CH₂ CH₃OCH₃O 1055 CH₂FO 3-CH₃SC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1056 CHF₂O 3-CH₃SC₆H₄ OH CH₂CH₂ CH₃O CH₃O 1057 CF₃O 3-CH₃SC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1058 CH₂FO3-CF₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1059 CHF₂O 3-CF₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O1060 CF₃O 3-CF₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1061 CH₂FO 3,4-F₂C₆H₃ O HCH₂CH₂ CH₃O CH₃O 1062 CHF₂O 3,4-F₂C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1063 CF₃O3,4-F₂C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1064 CH₂FO 3,4-Cl₂C₆H₃ O H CH₂CH₂ CH₃OCH₃O 1065 CHF₂O 3,4-Cl₂C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1066 CF₃O 3,4-Cl₂C₆H₃ OH CH₂CH₂ CH₃O CH₃O 1067 CH₂FO 3,4-Br₂C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1068CHF₂O 3,4-Br₂C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1069 CF₃O 3,4-Br₂C₆H₃ O H CH₂CH₂CH₃O CH₃O 1070 CH₂FO 3,4-(CH₃)₂C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1071 CHF₂O3,4-(CH₃)₂C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1072 CF₃O 3,4-(CH₃)₂C₆H₃ O H CH₂CH₂CH₃O CH₃O 1073 CH₂FO 3,4-(CH₃O)₂C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1074 CHF₂O3,4-(CH₃O)₂C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1075 CF₃O 3,4-(CH₃O)₂C₆H₃ O HCH₂CH₂ CH₃O CH₃O 1076 CH₂FO 3,4-(CF₃)₂C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1077CHF₂O 3,4-(CF₃)₂C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1078 CF₃O 3,4-(CF₃)₂C₆H₃ O HCH₂CH₂ CH₃O CH₃O 1079 CH₂FO 4-Cl-3-CH₃C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1080CHF₂O 4-Cl-3-CH₃C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1081 CF₃O 4-Cl-3-CH₃C₆H₃ O HCH₂CH₂ CH₃O CH₃O 1082 CH₂FO 3-Cl-4-CH₃C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1083CHF₂O 3-Cl-4-CH₃C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1084 CF₃O 3-Cl-4-CH₃C₆H₃ O HCH₂CH₂ CH₃O CH₃O 1085 CH₂FO 4-Cl-3-CH₃OC₆H₃ O H CH₂CH₂ CH₃O CH₃O 1086CHF₂O 4-Cl-3-CH₃OC₆H₃ O H CH₂CH₂ CH₃O CH₃O 1087 CF₃O 4-Cl-3-CH₃OC₆H₃ O HCH₂CH₂ CH₃O CH₃O 1088 CH₂FO 3-Cl-4-CH₃OC₆H₃ O H CH₂CH₂ CH₃O CH₃O 1089CHF₂O 3-Cl-4-CH₃OC₆H₃ O H CH₂CH₂ CH₃O CH₃O 1090 CF₃O 3-Cl-4-CH₃OC₆H₃ O HCH₂CH₂ CH₃O CH₃O 1091 CH₂FO 3,4-(OCH₂O)C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1092CHF₂O 3,4-(OCH₂O)C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1093 CF₃O 3,4-(OCH₂O)C₆H₃ O HCH₂CH₂ CH₃O CH₃O 1094 CH₂FO 3,4-(OCH₂CH₂O)C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1095CHF₂O 3,4-(OCH₂CH₂O)C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1096 CF₃O3,4-(OCH₂CH₂O)C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1097 CH₂FO 3,4-(OCF₂O)C₆H₃ O HCH₂CH₂ CH₃O CH₃O 1098 CHF₂O 3,4-(OCF₂O)C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1099CF₃O 3,4-(OCF₂O)C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1100 CH₂FO 3,4-(CH₂)₃C₆H₃ O HCH₂CH₂ CH₃O CH₃O 1101 CHF₂O 3,4-(CH₂)₃C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1102CF₃O 3,4-(CH₂)₃C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1103 CH₂FO 3,4-(CH₂)₄C₆H₃ O HCH₂CH₂ CH₃O CH₃O 1104 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1105CF₃O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1106 CH₂FO 3,4-(CH₂)₅C₆H₃ O HCH₂CH₂ CH₃O CH₃O 1107 CHF₂O 3,4-(CH₂)₅C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1108CF₃O 3,4-(CH₂)₅C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1109 CH₂FO C₆H₅ O CH₃CH(CH₃)CH₂ CH₃O CH₃O 1110 CHF₂O C₆H₅ O CH₃ CH(CH₃)CH₂ CH₃O CH₃O 1111CF₃O C₆H₅ O CH₃ CH(CH₃)CH₂ CH₃O CH₃O 1112 CH₂FO 4-CH₃C₆H₄ O CH₃CH(CH₃)CH₂ CH₃O CH₃O 1113 CHF₂O 4-CH₃C₆H₄ O CH₃ CH(CH₃)CH₂ CH₃O CH₃O1114 CF₃O 4-CH₃C₆H₄ O CH₃ CH(CH₃)CH₂ CH₃O CH₃O 1115 CH₂FO 4-ClC₆H₄ O CH₃CH(CH₃)CH₂ CH₃O CH₃O 1116 CHF₂O 4-ClC₆H₄ O CH₃ CH(CH₃)CH₂ CH₃O CH₃O 1117CF₃O 4-ClC₆H₄ O CH₃ CH(CH₃)CH₂ CH₃O CH₃O 1118 CH₂FO 3,4-(OCF₂O)C₆H₃ OCH₃ CH(CH₃)CH₂ CH₃O CH₃O 1119 CHF₂O 3,4-(OCF₂O)C₆H₃ O CH₃ CH(CH₃)CH₂CH₃O CH₃O 1120 CF₃O 3,4-(OCF₂O)C₆H₃ O CH₃ CH(CH₃)CH₂ CH₃O CH₃O 1121CH₂FO 3,4-(CH₂)₃C₆H₃ O CH₃ CH(CH₃)CH₂ CH₃O CH₃O 1122 CHF₂O3,4-(CH₂)₃C₆H₃ O CH₃ CH(CH₃)CH₂ CH₃O CH₃O 1123 CF₃O 3,4-(CH₂)₃C₆H₃ O CH₃CH(CH₃)CH₂ CH₃O CH₃O 1124 CH₂FO 3,4-(CH₂)₄C₆H₃ O CH₃ CH(CH₃)CH₂ CH₃OCH₃O 1125 CHF₂O 3,4-(CH₂)₄C₆H₃ O CH₃ CH(CH₃)CH₂ CH₃O CH₃O 1126 CF₃O3,4-(CH₂)₄C₆H₃ O H CH(CH₃)CH₂ CH₃O CH₃O 1127 CH₂FO C₆H₅ O H CH₂CH₂ CH₃OC₂H₅O 1128 CHF₂O C₆H₅ O H CH₂CH₂ CH₃O C₂H₅O 1129 CF₃O C₆H₅ O H CH₂CH₂CH₃O C₂H₅O 1130 CH₂FO 4-CH₃C₆H₄ O H CH₂CH₂ CH₃O C₂H₅O 1131 CHF₂O4-CH₃C₆H₄ O H CH₂CH₂ CH₃O C₂H₅O 1132 CF₃O 4-CH₃C₆H₄ O H CH₂CH₂ CH₃OC₂H₅O 1133 CH₂FO 4-ClC₆H₄ O H CH₂CH₂ CH₃O C₂H₅O 1134 CHF₂O 4-ClC₆H₄ O HCH₂CH₂ CH₃O C₂H₅O 1135 CF₃O 4-ClC₆H₄ O H CH₂CH₂ CH₃O C₂H₅O 1136 CH₂FO3,4-(OCF₂O)C₆H₃ O H CH₂CH₂ CH₃O C₂H₅O 1137 CHF₂O 3,4-(OCF₂O)C₆H₃ O HCH₂CH₂ CH₃O C₂H₅O 1138 CF₃O 3,4-(OCF₂O)C₆H₃ O H CH₂CH₂ CH₃O C₂H₅O 1139CH₂FO 3,4-(CH₂)₃C₆H₃ O H CH₂CH₂ CH₃O C₂H₅O 1140 CHF₂O 3,4-(CH₂)₃C₆H₃ O HCH₂CH₂ CH₃O C₂H₅O 1141 CF₃O 3,4-(CH₂)₃C₆H₃ O H CH₂CH₂ CH₃O C₂H₅O 1142CH₂FO 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O C₂H₅O 1143 CHF₂O 3,4-(CH₂)₄C₆H₃ O HCH₂CH₂ CH₃O C₂H₅O 1144 CF₃O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O C₂H₅O 1145CH₂FO C₆H₅ S H CH₂CH₂ CH₃O CH₃O 1146 CHF₂O C₆H₅ S H CH₂CH₂ CH₃O CH₃O1147 CF₃O C₆H₅ S H CH₂CH₂ CH₃O CH₃O 1148 CH₂FO 4-CH₃C₆H₄ S H CH₂CH₂ CH₃OCH₃O 1149 CHF₂O 4-CH₃C₆H₄ S H CH₂CH₂ CH₃O CH₃O 1150 CF₃O 4-CH₃C₆H₄ S HCH₂CH₂ CH₃O CH₃O 1151 CH₂FO 4-ClC₆H₄ S H CH₂CH₂ CH₃O CH₃O 1152 CHF₂O4-ClC₆H₄ S H CH₂CH₂ CH₃O CH₃O 1153 CF₃O 4-ClC₆H₄ S H CH₂CH₂ CH₃O CH₃O1154 CH₂FO 3,4-(OCF₂O)C₆H₃ S H CH₂CH₂ CH₃O CH₃O 1155 CHF₂O3,4-(OCF₂O)C₆H₃ S H CH₂CH₂ CH₃O CH₃O 1156 CF₃O 3,4-(OCF₂O)C₆H₃ S HCH₂CH₂ CH₃O CH₃O 1157 CH₂FO 3,4-(CH₂)₃C₆H₃ S H CH₂CH₂ CH₃O CH₃O 1158CHF₂O 3,4-(CH₂)₃C₆H₃ S H CH₂CH₂ CH₃O CH₃O 1159 CF₃O 3,4-(CH₂)₃C₆H₃ S HCH₂CH₂ CH₃O CH₃O 1160 CH₂FO 3,4-(CH₂)₄C₆H₃ S H CH₂CH₂ CH₃O CH₃O 1161CHF₂O 3,4-(CH₂)₄C₆H₃ S H CH₂CH₂ CH₃O CH₃O 1162 CF₃O 3,4-(CH₂)₄C₆H₃ S HCH₂CH₂ CH₃O CH₃O 1163 CH₂FS C₆H₅ O H CH₂CH₂ CH₃O CH₃O 1164 CHF₂S C₆H₅ OH CH₂CH₂ CH₃O CH₃O 1165 CF₃S C₆H₅ O H CH₂CH₂ CH₃O CH₃O 1166 CH₂FS4-CH₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1167 CHF₂S 4-CH₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O1168 CF₃S 4-CH₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1169 CH₂FS 4-ClC₆H₄ O H CH₂CH₂CH₃O CH₃O 1170 CHF₂S 4-ClC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1171 CF₃S 4-ClC₆H₄ OH CH₂CH₂ CH₃O CH₃O 1172 CH₂FS 3,4-(OCF₂O)C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1173CHF₂S 3,4-(OCF₂O)C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1174 CF₃S 3,4-(OCF₂O)C₆H₃ O HCH₂CH₂ CH₃O CH₃O 1175 CH₂FS 3,4-(CH₂)₃C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1176CHF₂S 3,4-(CH₂)₃C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1177 CF₃S 3,4-(CH₂)₃C₆H₃ O HCH₂CH₂ CH₃O CH₃O 1178 CH₂FS 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1179CHF₂S 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1180 CF₃S 3,4-(CH₂)₄C₆H₃ O HCH₂CH₂ CH₃O CH₃O 1181 CH≡CCH₂O C₆H₅ O H CH₂CH₂ CH₃O CH₃O 1182 CH≡CCH₂O4-CH₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1183 CH≡CCH₂O 4-C₂H₅C₆H₄ O H CH₂CH₂ CH₃OCH₃O 1184 CH≡CCH₂O 4-FC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1185 CH≡CCH₂O 4-ClC₆H₄ OH CH₂CH₂ CH₃O CH₃O 1186 CH≡CCH₂O 4-BrC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1187CH≡CCH₂O 4-CH₃OC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1188 CH≡CCH₂O 4-CF₃C₆H₄ O HCH₂CH₂ CH₃O CH₃O 1189 CH≡CCH₂O 4-(CH₃)₃CC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1190CH≡CCH₂O 3,4-Cl₂C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1191 CH≡CCH₂O 3,4-(CH₃)₂C₆H₃ OH CH₂CH₂ CH₃O CH₃O 1192 CH≡CCH₂O 3,4-(OCH₂O)C₆H₃ O H CH₂CH₂ CH₃O CH₃O1193 CH≡CCH₂O 3,4-(OCH₂CH₂O)C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1194 CH≡CCH₂O3,4-(OCF₂O)C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1195 CH≡CCH₂O 3,4-(CH₂)₃C₆H₃ O HCH₂CH₂ CH₃O CH₃O 1196 CH≡CCH₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1197CHBrF₂O 4-CH₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1198 CHBrF₂O 4-C₂H₅C₆H₄ O HCH₂CH₂ CH₃O CH₃O 1199 CHBrF₂O 4-ClC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1200 CHBrF₂O4-BrC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1201 CHBrF₂O 4-CF₃C₆H₄ O H CH₂CH₂ CH₃OCH₃O 1202 CHBrF₂O 4-CH₃OC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1203 CHBrF₂O4-CF₃OC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1204 CHBrF₂O 3,4-(CH₂)₃C₆H₃ O H CH₂CH₂CH₃O CH₃O 1205 CHBrF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1206 CHClF₂O4-CH₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1207 CHClF₂O 4-C₂H₅C₆H₄ O H CH₂CH₂ CH₃OCH₃O 1208 CHClF₂O 4-ClC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1209 CHClF₂O 4-BrC₆H₄ OH CH₂CH₂ CH₃O CH₃O 1210 CHClF₂O 4-CF₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1211CHClF₂O 4-CH₃OC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1212 CHClF₂O 4-CF₃OC₆H₄ O HCH₂CH₂ CH₃O CH₃O 1213 CHClF₂O 3,4-(CH₂)₃C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1214CHClF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1215 CCl≡CCH₂O 4-CH₃C₆H₄ O HCH₂CH₂ CH₃O CH₃O 1216 CCl≡CCH₂O 4-C₂H₅C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1217CCl≡CCH₂O 4-ClC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1218 CCl≡CCH₂O 4-BrC₆H₄ O HCH₂CH₂ CH₃O CH₃O 1219 CCl≡CCH₂O 4-CF₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1220CCl≡CCH₂O 4-CH₃OC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1221 CCl≡CCH₂O 4-CF₃OC₆H₄ O HCH₂CH₂ CH₃O CH₃O 1222 CCl≡CCH₂O 3,4-(CH₂)₃C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1223CCl≡CCH₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CH₃O 1224 CCl₂═CHCH₂O 4-CH₃C₆H₄O H CH₂CH₂ CH₃O CH₃O 1225 CCl₂═CHCH₂O 4-C₂H₅C₆H₄ O H CH₂CH₂ CH₃O CH₃O1226 CCl₂═CHCH₂O 4-ClC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1227 CCl₂═CHCH₂O 4-BrC₆H₄O H CH₂CH₂ CH₃O CH₃O 1228 CCl₂═CHCH₂O 4-CF₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O1229 CCl₂═CHCH₂O 4-CH₃OC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1230 CCl₂═CHCH₂O4-CF₃OC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1231 CCl₂═CHCH₂O 3,4-(CH₂)₃C₆H₃ O HCH₂CH₂ CH₃O CH₃O 1232 CCl₂═CHCH₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CH₃O1233 CH₂FCH₂O 4-CH₃C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1234 CH₂FCH₂O 4-C₂H₅C₆H₄ OH CH₂CH₂ CH₃O CH₃O 1235 CH₂FCH₂O 4-ClC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1236CH₂FCH₂O 4-BrC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1237 CH₂FCH₂O 4-CF₃C₆H₄ O HCH₂CH₂ CH₃O CH₃O 1238 CH₂FCH₂O 4-CH₃OC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1239CH₂FCH₂O 4-CF₃OC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1240 CH₂FCH₂O 3,4-(CH₂)₃C₆H₃ OH CH₂CH₂ CH₃O CH₃O 1241 CH₂FCH₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CH₃O1242 CClF₂O 2-naphthyl O H CH₂CH₂ CH₃O CH₃O 1243 CBrF₂O 2-naphthyl O HCH₂CH₂ CH₃O CH₃O 1244 CH₂FCH₂O 2-naphthyl O H CH₂CH₂ CH₃O CH₃O 1245CH≡CCH₂O 2-naphthyl O H CH₂CH₂ CH₃O CH₃O 1246 CH₂FO 4-NO₂C₆H₄ O H CH₂CH₂CH₃O CH₃O 1247 CHF₂O 4-NO₂C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1248 CF₃O 4-NO₂C₆H₄O H CH₂CH₂ CH₃O CH₃O 1249 CH═CCH₂O 4-NO₂C₆H₄ O H CH₂CH₂ CH₃O CH₃O 1250CH₂FO 4-(CH₃)₂CHC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1251 CHF₂O 4-(CH₃)₂CHC₆H₄ O HCH₂CH₂ CH₃O CH₃O 1252 CF₃O 4-(CH₃)₂CHC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1253CH≡CCH₂O 4-(CH₃)₂CHC₆H₄ O H CH₂CH₂ CH₃O CH₃O 1254 CH₂FO4-cyclopropylphenyl O H CH₂CH₂ CH₃O CH₃O 1255 CHF₂O 4-cyclopropylphenylO H CH₂CH₂ CH₃O CH₃O 1256 CF₃O 4-cyclopropylphenyl O H CH₂CH₂ CH₃O CH₃O1257 CH≡CCH₂O 4-cyclopropylphenyl O H CH₂CH₂ CH₃O CH₃O 1258 CHF₂O3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CH₃CH₂CH₂O 1259 CHF₂O 3,4-(CH₂)₄C₆H₃ O HCH₂CH₂ CH₃O (CH₃)₂CHO 1260 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃Ocyclopropoxy 1261 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O Cyclopropyl-methoxy 1262 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O butoxy 1263 CHF₂O3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O isobutoxy 1264 CHF₂O 3,4-(CH₂)₄C₆H₃ O HCH₂CH₂ CH₃O sec-butoxy 1265 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃Ot-butoxy 1266 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O allyloxy 1267 CHF₂O3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O 2-butenyloxy 1268 CHF₂O 3,4-(CH₂)₄C₆H₃ OH CH₂CH₂ CH₃O CH≡CCH₂O 1269 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O2-butynyloxy 1270 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O 2-pentynyl- oxy1271 CHF₂O 4-CH₃C₆H₄ O H CH₂CH₂ CH₃O 1-methyl-2- propynyloxy 1272 CHF₂O3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O 3-butynyloxy 1273 CHF₂O 3,4-(CH₂)₄C₆H₃ OH CH₂CH₂ CH₃O 4-pentynyl- oxy 1274 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃ONCCH₂O 1275 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CH₃S 1276 CHF₂O3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O C₂H₅S 1277 CHF₂O 3,4-(CH₂)₄C₆H₃ O HCH₂CH₂ CH₃O CH₂FO 1278 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CHF₂O 1279CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CF₃O 1280 CHF₂O 3,4-(CH₂)₄C₆H₃ O HCH₂CH₂ CH₃O CF₃CH₂O 1281 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O C₆H₄CH₂O1282 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CH₃CO₂ 1283 CHF₂O3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O C₂H₅CO₂ 1284 CHF₂O 3,4-(CH₂)₄C₆H₃ O HCH₂CH₂ CH₃O CH₃OCH₂O 1285 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O ethoxy-methoxy 1286 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CH₃NHCO₂ 1287 CHF₂O3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O 3,3-dichloro- allyloxy 1288 CHF₂O3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O 3-chloro-2- propynyl 1289 CHF₂O3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃CH₂CH₂O CH₃O 1290 CHF₂O 3,4-(CH₂)₄C₆H₃ O HCH₂CH₂ (CH₃)₂CHO CH₃O 1291 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ cyclopropoxyCH₃O 1292 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ Cyclopropyl- CH₃O methoxy 1293CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ butoxy CH₃O 1294 CHF₂O 3,4-(CH₂)₄C₆H₃ OH CH₂CH₂ isobutoxy CH₃O 1295 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ sec-butoxyCH₃O 1296 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ t-butoxy CH₃O 1297 CHF₂O3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ allyloxy CH₃O 1298 CHF₂O 3,4-(CH₂)₄C₆H₃ O HCH₂CH₂ 2-butenyl- CH₃O oxy 1299 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH≡CCH₂OCH₃O 1300 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ 2-butynyl- CH₃O oxy 1301 CHF₂O3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ 2-pentynyl CH₃O oxy 1302 CHF₂O 3,4-(CH₂)₄C₆H₃O H CH₂CH₂ 1-methyl-2- CH₃O propynyloxy 1303 CHF₂O 3,4(CH₂)₄C₆H₃ O HCH₂CH₂ 3-butynyl- CH₃O oxy 1304 CHF₂O 3,4(CH₂)₄C₆H₃ O H CH₂CH₂4-pentynyl CH₃O oxy 1305 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ NCCH₂O CH₃O1306 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃S CH₃O 1307 CHF₂O 3,4-(CH₂)₄C₆H₃O H CH₂CH₂ C₂H₅S CH₃O 1308 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₂FO CH₃O1309 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CHF₂O CH₃O 1310 CHF₂O3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CF₃O CH₃O 1311 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂CF₃CH₂O CH₃O 1312 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ OH CH₃O 1313 CHF₂O3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃CO₂ CH₃O 1314 CHF₂O 3,4-(CH₂)₄C₆H₃ O HCH₂CH₂ C₂H₅CO₂ CH₃O 1315 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃OCH₂O CH₃O1316 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ ethoxy- CH₃O methoxy 1317 CHF₂O3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃NHCO₂ CH₃O 1318 CHF₂O 3,4-(CH₂)₄C₆H₃ O HCH₂CH₂ 3,3-dichloro CH₃O allyloxy 1319 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂3-chloro-2- CH₃O propynyl 1320 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ C₂H₅OCH₃O 1321 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ C₂H₅O C₂H₅O 1322 CHF₂O3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ C₂H₅O CH₃CH₃CH₃O 1323 CHF₂O 3,4-(CH₂)₄C₆H₃ O HCH₂CH₂ C₂H₅O butoxy 1324 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ C₂H₅O allyloxy1325 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ C₂H₅O CH≡CCH₂O 1326 CHF₂O3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ C₂H₅O 2-butynyl oxy 1327 CHF₂O 3,4-(CH₂)₄C₆H₃O H CH₂CH₂ C₂H₅O 3-butynyl oxy 1328 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂C₂H₅O NCCH₂O 1329 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ C₂H₅O CH₃S 1330 CHF₂O3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ C₂H₅O CF₃O 1331 CHF₂O 3,4-(CH₂)₄C₆H₃ O HCH₂CH₂ propoxy propoxy 1332 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ propoxy(CH₃)₂CHO 1333 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ propoxy cyclopropylmethoxy 1334 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ propoxy butoxy 1335 CHF₂O3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ propoxy allyloxy 1336 CHF₂O 3,4-(CH₂)₄C₆H₃ O HCH₂CH₂ propoxy CH≡CCH₂O 1337 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ propoxy2-butynyl oxy 1338 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ propoxy 3-butynyl oxy1339 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ propoxy NCCH₂O 1340 CHF₂O3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ propoxy CH₃S 1341 CHF₂O 3,4-(CH₂)₄C₆H₃ O HCH₂CH₂ propoxy CF₃O 1342 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ propoxyCCl≡CCH₂O 1343 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ (CH₃)₂CHO CH≡CCH₂O 1344CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ cyclopropyl- CH≡CCH₂O methoxy 1345 CHF₂O3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ butoxy CH≡CCH₂O 1346 CHF₂O 3,4-(CH₂)₄C₆H₃ O HCH₂CH₂ allyloxy CH≡CCH₂O 1347 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH≡CCH₂OCH≡CCH₂O 1348 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ 2-butynyl CH≡CCH₂O oxy1349 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ 3-butynyl CH≡CCH₂O oxy 1350 CHF₂O3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ NCCH₂O CH≡CCH₂O 1351 CHF₂O 3,4-(CH₂)₄C₆H₃ O HCH₂CH₂ CH₃S CH≡CCH₂O 1352 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CF₃O CH≡CCH₂O1353 CHF₂O 4-CH₃C₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1354 CHF₂O 4-C₂H₅C₆H₄ O HCH₂CH₂ CH₃O CH≡CCH₂O 1355 CHF₂O 4-ClC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1356CHF₂O 4-BrC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1357 CHF₂O 4-CF₃C₆H₄ O H CH₂CH₂CH₃O CH≡CCH₂O 1358 CHF₂O 4-CH₃OC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1359 CHF₂O4-CF₃OC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1360 CHF₂O 3,4-(CH₂)₃C₆H₃ O H CH₂CH₂CH₃O CH≡CCH₂O 1361 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CH≡CCH₂O 1362CH₂FO 4-CH₃C₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1363 CF₃O 4-CH₃C₆H₄ O H CH₂CH₂CH₃O CH≡CCH₂O 1364 CH≡CCH₂O 4-CH₃C₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1365CH₂FO 4-ClC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1366 CF₃O 4-ClC₆H₄ O H CH₂CH₂CH₃O CH≡CCH₂O 1367 CH≡CCH₂O 4-ClC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1368 CH₂FO3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O CH≡CCH₂O 1369 CF₃O 3,4-(CH₂)₄C₆H₃ O HCH₂CH₂ CH₃O CH≡CCH₂O 1370 CH≡CCH₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃OCH≡CCH₂O 1371 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃O OH 1372 CH₂FO4-C₂H₅C₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1373 CF₃O 4-C₂H₅C₆H₄ O H CH₂CH₂ CH₃OCH≡CCH₂O 1374 CH≡CCH₂O 4-C₂H₅C₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1375 CH₂FO4-BrC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1376 CF₃O 4-BrC₆H₄ O H CH₂CH₂ CH₃OCH≡CCH₂O 1377 CH≡CCH₂O 4-BrC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1378 CH₂FO4-CF₃C₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1379 CF₃O 4-CF₃C₆H₄ O H CH₂CH₂ CH₃OCH≡CCH₂O 1380 CH≡CCH₂O 4-CF₃C₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1381 CH₂FO4-CH₃OC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1382 CF₃O 4-CH₃OC₆H₄ O H CH₂CH₂ CH₃OCH≡CCH₂O 1383 CH≡CCH₂O 4-CH₃OC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1384 CH₂FO4-CF₃OC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1385 CF₃O 4-CF₃OC₆H₄ O H CH₂CH₂ CH₃OCH≡CCH₂O 1386 CH≡CCH₂O 4-CF₃OC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1387 CH₂FOC₆H₅ O H CH₂CH₂ CH₃O CH≡CCH₂O 1388 CHF₂O C₆H₅ O H CH₂CH₂ CH₃O CH≡CCH₂O1389 CF₃O C₆H₅ O H CH₂CH₂ CH₃O CH≡CCH₂O 1390 CH≡CCH₂O C₆H₅ O H CH₂CH₂CH₃O CH≡CCH₂O 1391 CH₂FO 4-FC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1392 CHF₂O4-FC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1393 CF₃O 4-FC₆H₄ O H CH₂CH₂ CH₃OCH≡CCH₂O 1394 CH≡CCH₂O 4-FC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1395 CH₂FO4-CH₃CH₂CH₂C₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1396 CHF₂O 4-CH₃CH₂CH₂C₆H₄ O HCH₂CH₂ CH₃O CH≡CCH₂O 1397 CF₃O 4-CH₃CH₂CH₂C₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O1398 CH≡CCH₂O 4-CH₃CH₂CH₂C₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1399 CH₂FO4-(CH₃)₂CHC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1400 CHF₂O 4-(CH₃)₂CHC₆H₄ O HCH₂CH₂ CH₃O CH≡CCH₂O 1401 CF₃O 4-(CH₃)₂CHC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O1402 CH≡CCH₂O 4-(CH₃)₂CHC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1403 CH₂FO4-cyclopropylphenyl O H CH₂CH₂ CH₃O CH≡CCH₂O 1404 CHF₂O4-cyclopropylphenyl O H CH₂CH₂ CH₃O CH≡CCH₂O 1405 CF₃O4-cyclopropylphenyl O H CH₂CH₂ CH₃O CH≡CCH₂O 1406 CH≡CCH₂O4-cyclopropylphenyl O H CH₂CH₂ CH₃O CH≡CCH₂O 1407 CH₂FO 4-(CH₃)₃CC₆H₄ OH CH₂CH₂ CH₃O CH≡CCH₂O 1408 CHF₂O 4-(CH₃)₃CC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O1409 CF₃O 4-(CH₃)₃CC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1410 CH≡CCH₂O4-(CH₃)₃CC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1411 CH₂FO 4-CH₃SC₆H₄ O H CH₂CH₂CH₃O CH≡CCH₂O 1412 CHF₂O 4-CH₃SC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1413 CF₃O4-CH₃SC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1414 CH≡CCH₂O 4-CH₃SC₆H₄ O H CH₂CH₂CH₃O CH≡CCH₂O 1415 CH₂FO 4-CH≡CC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1416 CHF₂O4-CH≡CC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1417 CF₃O 4-CH≡CC₆H₄ O H CH₂CH₂ CH₃OCH≡CCH₂O 1418 CH≡CCH₂O 4-CH≡CC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1419 CH₂FO4-N≡CC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1420 CHF₂O 4-N≡CC₆H₄ O H CH₂CH₂ CH₃OCH≡CCH₂O 1421 CF₃O 4-N≡CC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1422 CH≡CCH₂O4-N≡CC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1423 CH₂FO 4-CH₂≡CHC₆H₄ O H CH₂CH₂CH₃O CH≡CCH₂O 1424 CHF₂O 4-CH₂≡CHC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1425 CF₃O4-CH₂≡CHC₆H₄ O H CH₂CH₂ CH₃O CH≡CCH₂O 1426 CH≡CCH₂O 4-CH₂≡CHC₆H₄ O HCH₂CH₂ CH₃O CH≡CCH₂O 1427 CHF₂O 3,4-F₂C₆H₃ O H CH₂CH₂ CH₃O CH≡CCH₂O 1428CH≡CCH₂O 3,4-F₂C₆H₃ O H CH₂CH₂ CH₃O CH≡CCH₂O 1429 CHF₂O 3,4-Cl₂C₆H₃ O HCH₂CH₂ CH₃O CH≡CCH₂O 1430 CH≡CCH₂O 3,4-Cl₂C₆H₃ O H CH₂CH₂ CH₃O CH≡CCH₂O1431 CHF₂O 3,4-(CH₃)₂C₆H₃ O H CH₂CH₂ CH₃O CH≡CCH₂O 1432 CH≡CCH₂O3,4-(CH₃)₂C₆H₃ O H CH₂CH₂ CH₃O CH≡CCH₂O 1433 CHF₂O 3-F-4-CH₃C₆H₃ O HCH₂CH₂ CH₃O CH≡CCH₂O 1434 CH≡CCH₂O 3-F-4-CH₃C₆H₃ O H CH₂CH₂ CH₃OCH≡CCH₂O 1435 CHF₂O 3-Cl-4-CH₃C₆H₃ O H CH₂CH₂ CH₃O CH≡CCH₂O 1436CH≡CCH₂O 3-Cl-4-CH₃C₆H₃ O H CH₂CH₂ CH₃O CH≡CCH₂O 1437 CHF₂O 4-Cl-3-FC₆H₃O H CH₂CH₂ CH₃O CH≡CCH₂O 1438 CH≡CCH₂O 4-Cl-3-FC₆H₃ O H CH₂CH₂ CH₃OCH≡CCH₂O 1439 CHF₂O 3,4-Cl₂C₆H₃ O H CH₂CH₂ CH₃O CH≡CCH₂O 1440 CH≡CCH₂O3,4-Cl₂C₆H₃ O H CH₂CH₂ CH₃O CH≡CCH₂O 1441 CHF₂O 3-Cl-4-CH₃C₆H₃ O HCH(CH₃)CH₂ CH₃O CH≡CCH₂O 1442 CH≡CCH₂O 3-Cl-4-CH₃C₆H₃ O H CH(CH₃)CH₂CH₃O CH≡CCH₂O 1443 CHF₂O 3,4-Cl₂C₆H₃ O H CH(CH₃)CH₂ CH₃O CH≡CCH₂O 1444CH≡CCH₂O 3,4-Cl₂C₆H₃ O H CH(CH₃)CH₂ CH₃O CH≡CCH₂O 1445 CHF₂O 4-CH₃C₆H₄ SH CH₂CH₂ CH₃O CH≡CCH₂O 1446 CHF₂O 4-ClC₆H₄ S H CH₂CH₂ CH₃O CH≡CCH₂O 1447CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ Cl CH₃O 1448 CHF₂O 3,4-(CH₂)₄C₆H₃ O HCH₂CH₂ CH₃ CH₃O 1449 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ CH₃CH₂ CH₃O 1450CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂ OCH₂CH₂O 1451 CHF₂O 4-CH₃C₆H₄ O H CH₂CH₂CH₃O C₆H₅CH₂O 1452 CHF₂O 4-CH₃C₆H₄ O H CH₂CH₂ CH₃O OH 1453 CHF₂O4-ClC₆H₄ O H CH₂CH₂ CH₃O C₆H₅CH₂O 1454 CHF₂O 4-ClC₆H₄ O H CH₂CH₂ CH₃O OH1455 CH≡CCH₂O 4-CH₃C₆H₄ O H CH₂CH₂ CH₃O C₆H₅CH₂O 1456 CH≡CCH₂O 4-CH₃C₆H₄O H CH₂CH₂ CH₃O OH 1457 CH≡CCH₂O 4-ClC₆H₄ O H CH₂CH₂ CH₃O C₆H₅CH₂O 1458CH≡CCH₂O 4-ClC₆H₄ O H CH₂CH₂ CH₃O OH 1459 CHF₂O 4-CH₃C₆H₄ O CH₃ CH₂CH₂CH₃O CH≡CCH₂O 1460 CHF₂O 4-CH₃C₆H₄ O ethyl CH₂CH₂ CH₃O CH≡CCH₂O 1461CHF₂O 4-CH₃C₆H₄ O propyl CH₂CH₂ CH₃O CH≡CCH₂O 1462 CHF₂O 4-ClC₆H₄ O CH₃CH₂CH₂ CH₃O CH≡CCH₂O 1463 CHF₂O 3,4-(CH₂)₄C₆H₃ O CH₃ CH₂CH₂ CH₃OCH≡CCH₂O 1464 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH(CH₃)CH₂ CH₃O CH₃O 1465 CHF₂O4-CH₃C₆H₄ O H CH(CH₃)CH₂ CH₃O CH≡CCH₂O 1466 CHF₂O 4-ClC₆H₄ O HCH(CH₃)CH₂ CH₃O CH≡CCH₂O 1467 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH(CH₃) CH₃OCH₃O 1468 CHF₂O 4-CH₃C₆H₄ O H CH₂CH(CH₃) CH₃O CH≡CCH₂O 1469 CHF₂O4-ClC₆H₄ O H CH₂CH(CH₃) CH₃O CH≡CCH₂O 1470 CHF₂O 4-CH₃C₆H₄ O H CH₂CHFCH₃O CH≡CCH₂O 1471 CHF₂O 4-CH₃C₆H₄ O H CH₂CHCl CH₃O CH≡CCH₂O 1472 CHF₂O4-CH₃C₆H₄ O H CH₂CH(OCH₃) CH₃O CH≡CCH₂O 1473 CHF₂O 4-CH₃C₆H₄ O HCH₂CH(CN) CH₃O CH≡CCH₂O 1474 CHF₂O 4-CH₃C₆H₄ O H CH(CN)CH₂ CH₃O CH≡CCH₂O1475 CHF₂O 3,4-(CH₂)₄C₆H₃ O H CH₂CH₂CH₂ CH₃O CH₃O 1476 CHF₂O 4-CH₃C₆H₄ OH CH₂CH₂CH₂ CH₃O CH₃O 1477 CHF₂O 4-CH₃C₆H₄ O H CH₂CH₂CH₂ CH₃O CH≡CCH₂O1478 CHF₂O 4-ClC₆H₄ O H CH₂CH₂CH₂ CH₃O CH≡CCH₂O 2001 CH₂FO 2-thienyl O HCH₂CH₂ CH₃O CH₃O 2002 CHF₂O 2-thienyl O H CH₂CH₂ CH₃O CH₃O 2003 CF₃O2-thienyl O H CH₂CH₂ CH₃O CH₃O 2004 CH₂FO 3-thienyl O H CH₂CH₂ CH₃O CH₃O2005 CHF₂O 3-thienyl O H CH₂CH₂ CH₃O CH₃O 2006 CF₃O 3-thienyl O H CH₂CH₂CH₃O CH₃O 2007 CH₂FO 2-(4-methylthienyl) O H CH₂CH₂ CH₃O CH₃O 2008 CHF₂O2-(4-methylthienyl) O H CH₂CH₂ CH₃O CH₃O 2009 CF₃O 2-(4-methylthienyl) OH CH₂CH₂ CH₃O CH₃O 2010 CH₂FO 2-(5-methylthienyl) O H CH₂CH₂ CH₃O CH₃O2011 CHF₂O 2-(5-methylthienyl) O H CH₂CH₂ CH₃O CH₃O 2012 CF₃O2-(5-methylthienyl) O H CH₂CH₂ CH₃O CH₃O 2013 CH₂FO 2-(4-chlorothienyl)O H CH₂CH₂ CH₃O CH₃O 2014 CHF₂O 2-(4-chlorothienyl) O H CH₂CH₂ CH₃O CH₃O2015 CF₃O 2-(4-chlorothienyl) O H CH₂CH₂ CH₃O CH₃O 2016 CH₂FO2-(5-trifluoromethyl O H CH₂CH₂ CH₃O CH₃O thienyl) 2017 CHF₂O2-(5-trifluoromethyl O H CH₂CH₂ CH₃O CH₃O thienyl) 2018 CF₃O2-(5-trifluoromethyl O H CH₂CH₂ CH₃O CH₃O thienyl) 2019 CH₂FO 2-furyl OH CH₂CH₂ CH₃O CH₃O 2020 CHF₂O 2-furyl O H CH₂CH₂ CH₃O CH₃O 2021 CF₃O2-furyl O H CH₂CH₂ CH₃O CH₃O 2022 CH₂FO 3-furyl O H CH₂CH₂ CH₃O CH₃O2023 CHF₂O 3-furyl O H CH₂CH₂ CH₃O CH₃O 2024 CF₃O 3-furyl O H CH₂CH₂CH₃O CH₃O 2025 CH₂FO 2-(5-methyfuryl) O H CH₂CH₂ CH₃O CH₃O 2026 CHF₂O2-(5-methyfuryl) O H CH₂CH₂ CH₃O CH₃O 2027 CF₃O 2-(5-methyfuryl) O HCH₂CH₂ CH₃O CH₃O 2028 CH₂FO 2-pyridyl O H CH₂CH₂ CH₃O CH₃O 2029 CHF₂O2-pyridyl O H CH₂CH₂ CH₃O CH₃O 2030 CF₃O 2-pyridyl O H CH₂CH₂ CH₃O CH₃O2031 CH₂FO 2-(5-methylpyridyl) O H CH₂CH₂ CH₃O CH₃O 2032 CHF₂O2-(5-methylpyridyl) O H CH₂CH₂ CH₃O CH₃O 2033 CF₃O 2-(5-methylpyridyl) OH CH₂CH₂ CH₃O CH₃O 2034 CH₂FO 2-(5-trifluoromethyl O H CH₂CH₂ CH₃O CH₃Opyridyl) 2035 CHF₂O 2-(5-trifluoromethyl O H CH₂CH₂ CH₃O CH₃O pyridyl)2036 CF₃O 2-(5-trifluoromethyl O H CH₂CH₂ CH₃O CH₃O pyridyl) 2037 CH₂FO2-pyrimidinyl O H CH₂CH₂ CH₃O CH₃O 2038 CHF₂O 2-pyrimidinyl O H CH₂CH₂CH₃O CH₃O 2039 CF₃O 2-pyrimidinyl O H CH₂CH₂ CH₃O CH₃O 2040 CH₂FO4-pyrimidinyl O H CH₂CH₂ CH₃O CH₃O 2041 CHF₂O 4-pyrimidinyl O H CH₂CH₂CH₃O CH₃O 2042 CF₃O 4-pyrimidinyl O H CH₂CH₂ CH₃O CH₃O 2043 CH₂FO2-pyrazinyl O H CH₂CH₂ CH₃O CH₃O 2044 CHF₂O 2-pyrazinyl O H CH₂CH₂ CH₃OCH₃O 2045 CF₃O 2-pyrazinyl O H CH₂CH₂ CH₃O CH₃O 2046 CH₂FO 2-thiazolyl OH CH₂CH₂ CH₃O CH₃O 2047 CHF₂O 2-thiazolyl O H CH₂CH₂ CH₃O CH₃O 2048 CF₃O2-thiazolyl O H CH₂CH₂ CH₃O CH₃O 2049 CH₂FO 2-(5-methylthiazolyl) O HCH₂CH₂ CH₃O CH₃O 2050 CHF₂O 2-(5-methylthiazolyl) O H CH₂CH₂ CH₃O CH₃O2051 CF₃O 2-(5-methylthiazolyl) O H CH₂CH₂ CH₃O CH₃O 2052 CH₂FO2-(3-methylthiazolyl) O H CH₂CH₂ CH₃O CH₃O 2053 CHF₂O2-(3-methylthiazolyl) O H CH₂CH₂ CH₃O CH₃O 2054 CF₃O2-(3-methylthiazolyl) O H CH₂CH₂ CH₃O CH₃O 2055 CH₂FO1-(4-methylpyrazolyl) O H CH₂CH₂ CH₃O CH₃O 2056 CHF₂O1-(4-methylpyrazolyl) O H CH₂CH₂ CH₃O CH₃O 2057 CF₃O1-(4-methylpyrazolyl) O H CH₂CH₂ CH₃O CH₃O 2058 CH₂FO 2-thienyl O HCH₂CH₂ CH₃CH₂O CH₃O 2059 CHF₂O 2-thienyl O H CH₂CH₂ CH₃CH₂O CH₃O 2060CF₃O 2-thienyl O H CH₂CH₂ CH₃CH₂O CH₃O 2061 CH₂FO 3-thienyl O H CH₂CH₂CH₃CH₂O CH₃O 2062 CHF₂O 3-thienyl O H CH₂CH₂ CH₃CH₂O CH₃O 2063 CF₃O3-thienyl O H CH₂CH₂ CH₃CH₂O CH₃O 2064 CH₂FO 2-thienyl S H CH₂CH₂ CH₃OCH₃O 2065 CHF₂O 2-thienyl S H CH₂CH₂ CH₃O CH₃O 2066 CF₃O 2-thienyl S HCH₂CH₂ CH₃O CH₃O 2067 CH₂FO 3-thienyl S H CH₂CH₂ CH₃O CH₃O 2068 CHF₂O3-thienyl S H CH₂CH₂ CH₃O CH₃O 2069 CF₃O 3-thienyl S H CH₂CH₂ CH₃O CH₃O2070 CH₂FO 2-(5-methylpyridyl) O H CH₂CH₂ CH₃CH₂O CH₃O 2071 CHF₂O2-(5-methylpyridyl) O H CH₂CH₂ CH₃CH₂O CH₃O 2072 CF₃O 2-(5methylpyridyl)O H CH₂CH₂ CH₃CH₂O CH₃O 2073 CH₂FO 1-naphthyl O H CH₂CH₂ CH₃O CH₃O 2074CHF₂O 1-naphthyl O H CH₂CH₂ CH₃O CH₃O 2075 CF₃O 1-naphthyl O H CH₂CH₂CH₃O CH₃O 2076 CH₂FO 2-naphthyl O H CH₂CH₂ CH₃O CH₃O 2077 CHF₂O2-naphthyl O H CH₂CH₂ CH₃O CH₃O 2078 CF₃O 2-naphthyl O H CH₂CH₂ CH₃OCH₃O 2079 CH₂FO 2-naplithyl S H CH₂CH₂ CH₃O CH₃O 2080 CHF₂O 2-naphthyl SH CH₂CH₂ CH₃O CH₃O 2081 CF₃O 2-naphthyl S H CH₂CH₂ CH₃O CH₃O 2082 CH₂FO5-benzofuryl O H CH₂CH₂ CH₃O CH₃O 2083 CHF₂O 5-benzofuryl O H CH₂CH₂CH₃O CH₃O 2084 CF₃O 5-benzofuryl O H CH₂CH₂ CH₃O CH₃O 2085 CH₂FO6-benzofuryl O H CH₂CH₂ CH₃O CH₃O 2086 CHF₂O 6-benzofuryl O H CH₂CH₂CH₃O CH₃O 2087 CF₃O 6-benzofuryl O H CH₂CH₂ CH₃O CH₃O 2088 CH₂FO5-benzothienyl O H CH₂CH₂ CH₃O CH₃O 2089 CHF₂O 5-benzothienyl O H CH₂CH₂CH₃O CH₃O 2090 CF₃O 5-benzothienyl O H CH₂CH₂ CH₃O CH₃O 2091 CH₂FO6-benzothienyl O H CH₂CH₂ CH₃O CH₃O 2092 CHF₂O 6-benzothienyl O H CH₂CH₂CH₃O CH₃O 2093 CF₃O 6-benzothienyl O H CH₂CH₂ CH₃O CH₃O 2094 CH₂FO5-benzothiazolyl O H CH₂CH₂ CH₃O CH₃O 2095 CHF₂O 5-benzothiazolyl O HCH₂CH₂ CH₃O CH₃O 2096 CF₃O 5-benzothiazolyl O H CH₂CH₂ CH₃O CH₃O 2097CH₂FO 6-benzothiazolyl O H CH₂CH₂ CH₃O CH₃O 2098 CHF₂O 6-benzothiazolylO H CH₂CH₂ CH₃O CH₃O 2099 CF₃O 6-benzothiazolyl O H CH₂CH₂ CH₃O CH₃O2100 CH₂FO 2-benzothiazolyl O H CH₂CH₂ CH₃O CH₃O 2101 CHF₂O2-benzothiazolyl O H CH₂CH₂ CH₃O CH₃O 2102 CF₃O 2-benzothiazolyl O HCH₂CH₂ CH₃O CH₃O 2103 CH₂FO 2-benzothienyl O H CH₂CH₂ CH₃O CH₃O 2104CHF₂O 2-benzothienyl O H CH₂CH₂ CH₃O CH₃O 2105 CF₃O 2-benzothienyl O HCH₂CH₂ CH₃O CH₃O 2106 CH₂FO 2-benzofuryl O H CH₂CH₂ CH₃O CH₃O 2107 CHF₂O2-benzofuryl O H CH₂CH₂ CH₃O CH₃O 2108 CF₃O 2-benzofuryl O H CH₂CH₂ CH₃OCH₃O 2109 CH₂FO 3-benzofuryl O H CH₂CH₂ CH₃O CH₃O 2110 CHF₂O3-benzofuryl O H CH₂CH₂ CH₃O CH₃O 2111 CF₃O 3-benzofuryl O H CH₂CH₂ CH₃OCH₃O 2112 CH₂FO benzo-1,2,3-thiazol- O H CH₂CH₂ CH₃O CH₃O 5-yl 2113CHF₂O benzo-1,2,3-thiazol- O H CH₂CH₂ CH₃O CH₃O 5-yl 2114 CF₃Obenzo-1,2,3-thiazol- O H CH₂CH₂ CH₃O CH₃O 5-yl 2115 CH₂FO2-benzimidazolyl O H CH₂CH₂ CH₃O CH₃O 2116 CHF₂O 2-benzimidazolyl O HCH₂CH₂ CH₃O CH₃O 2117 CF₃O 2-benzimidazolyl O H CH₂CH₂ CH₃O CH₃O 2118CH₂FO 2-(1-methylbenzimi- O H CH₂CH₂ CH₃O CH₃O dazolyl) 2119 CHF₂O2-(1-methylbenzimi- O H CH₂CH₂ CH₃O CH₃O dazolyl) 2120 CF₃O2-(1-methylbenzimi- O H CH₂CH₂ CH₃O CH₃O dazolyl) 2121 CH≡CCH₂O2-(5-methylthienyl) O H CH₂CH₂ CH₃O CH₃O 2122 CH≡CCH₂O2-(5-trifluorometh- O H CH₂CH₂ CH₃O CH₃O ylthienyl) 2123 CH≡CCH₂O2-(5-methylfuryl) O H CH₂CH₂ CH₃O CH₃O 2124 CH≡CCH₂O 2-(5-trifluorometh-O H CH₂CH₂ CH₃O CH₃O ylpyridyl) 2125 CH≡CCH₂O 2-naphthyl O H CH₂CH₂ CH₃OCH₃O 2126 CH₂FO 2-thienyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2127 CHF₂O 2-thienylO H CH₂CH₂ CH₃O CH≡CCH₂O 2128 CF₃O 2-thienyl O H CH₂CH₂ CH₃O CH≡CCH₂O2129 CH₂FO 3-thienyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2130 CHF₂O 3-thienyl O HCH₂CH₂ CH₃O CH≡CCH₂O 2131 CF₃O 3-thienyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2132CH₂FO 2-(4-methylthienyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2133 CHF₂O2-(4-methylthienyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2134 CF₃O2-(4-methylthienyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2135 CH₂FO2-(5-methylthienyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2136 CHF₂O2-(5-methylthienyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2137 CF₃O2-(5-methylthienyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2138 CH₂FO2-(5-chlorothienyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2139 CHF₂O2-(5-chlorothienyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2140 CF₃O2-(5-chlorothienyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2141 CH₂FO2-(5-trifluoromethyl O H CH₂CH₂ CH₃O CH≡CCH₂O thienyl) 2142 CHF₂O2-(5-trifluoromethyl O H CH₂CH₂ CH₃O CH≡CCH₂O thienyl) 2143 CF₃O2-(5-trifluoromethyl O H CH₂CH₂ CH₃O CH≡CCH₂O thienyl) 2144 CH₂FO2-furyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2145 CHF₂O 2-furyl O H CH₂CH₂ CH₃OCH≡CCH₂O 2146 CF₃O 2-furyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2147 CH₂FO 3-furyl OH CH₂CH₂ CH₃O CH≡CCH₂O 2148 CHF₂O 3-furyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2149CF₃O 3-furyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2150 CH₂FO 2-(5-methylfuryl) O HCH₂CH₂ CH₃O CH≡CCH₂O 2151 CHF₂O 2-(5-methylfuryl) O H CH₂CH₂ CH₃OCH≡CCH₂O 2152 CF₃O 2-(5-methylfuryl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2153 CH₂FO2-pyridyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2154 CHF₂O 2-pyridyl O H CH₂CH₂ CH₃OCH≡CCH₂O 2155 CF₃O 2-pyridyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2156 CH₂FO2-(5-methylpyridyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2157 CHF₂O2-(5-methylpyridyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2158 CF₃O2-(5-methylpyridyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2159 CH₂FO2-(5-trifluoromethyl O H CH₂CH₂ CH₃O CH≡CCH₂O pyridyl) 2160 CHF₂O2-(5-trifluoromethyl O H CH₂CH₂ CH₃O CH≡CCH₂O pyridyl) 2161 CF₃O2-(5-trifluoromethyl O H CH₂CH₂ CH₃O CH≡CCH₂O pyridyl) 2162 CH₂FO2-pyrimidinyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2163 CHF₂O 2-pyrimidinyl O HCH₂CH₂ CH₃O CH≡CCH₂O 2164 CF₃O 2-pyrimidinyl O H CH₂CH₂ CH₃O CH≡CCH₂O2165 CH₂FO 4-pyrimidinyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2166 CHF₂O4-pyrimidinyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2167 CF₃O 4-pyrimidinyl O HCH₂CH₂ CH₃O CH≡CCH₂O 2168 CH₂FO 2-pyrazinyl O H CH₂CH₂ CH₃O CH≡CCH₂O2169 CHF₂O 2-pyrazinyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2170 CF₃O 2-pyrazinyl OH CH₂CH₂ CH₃O CH≡CCH₂O 2171 CH₂FO 2-thiazolyl O H CH₂CH₂ CH₃O CH≡CCH₂O2172 CHF₂O 2-thiazolyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2173 CF₃O 2-thiazolyl OH CH₂CH₂ CH₃O CH≡CCH₂O 2174 CH₂FO 2-(5-methylthiazolyl) O H CH₂CH₂ CH₃OCH≡CCH₂O 2175 CHF₂O 2-(5-methylthiazolyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2176CF₃O 2-(5-methylthiazolyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2177 CH₂FO3-(3-methylpyrazolyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2178 CHF₂O3-(3-methylpyrazolyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2179 CF₃O3-(3-methylpyrazolyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2180 CH₂FO1-(4-methylpyrazolyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2181 CHF₂O1-(4-methylpyrazolyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2182 CF₃O1-(4-methylpyrazolyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2183 CH₂FO 2-thienyl O HCH(CH₃)CH₂ CH₃O CH₃O 2184 CHF₂O 2-thienyl O H CH(CH₃)CH₂ CH₃O CH₃O 2185CF₃O 2-thienyl O H CH(CH₃)CH₂ CH₃O CH₃O 2186 CH₂FO 3-thienyl O HCH(CH₃)CH₂ CH₃O CH₃O 2187 CHF₂O 3-thienyl O H CH(CH₃)CH₂ CH₃O CH₃O 2188CF₃O 3-thienyl O H CH(CH₃)CH₂ CH₃O CH₃O 2189 CH₂FO 2-naphthyl O HCH(CH₃)CH₂ CH₃O CH₃O 2190 CHF₂O 2-naphthyl O H CH(CH₃)CH₂ CH₃O CH₃O 2191CF₃O 2-naphthyl O H CH(CH₃)CH₂ CH₃O CH₃O 2192 CH₂FO 2-naphthyl O CH₃CH₂CH₂ CH₃O CH₃O 2193 CHF₂O 2-naphthyl O CH₃ CH₂CH₂ CH₃O CH₃O 2194 CF₃O2-naphthyl O CH₃ CH₂CH₂ CH₃O CH₃O 2195 CH₂FO 2-thienyl O CH₃ CH₂CH₂ CH₃OCH₃O 2196 CHF₂O 2-thienyl O CH₃ CH₂CH₂ CH₃O CH₃O 2197 CF₃O 2-thienyl OCH₃ CH₂CH₂ CH₃O CH₃O 2198 CH₂FO 1-naphthyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2199CHF₂O 1-naphthyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2200 CF₃O 1-naphthyl O HCH₂CH₂ CH₃O CH≡CCH₂O 2201 CH₂FO 2-naphthyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2202CHF₂O 2-naphthyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2203 CF₃O 2-naphthyl O HCH₂CH₂ CH₃O CH≡CCH₂O 2204 CH₂FO 2-naphthyl S H CH₂CH₂ CH₃O CH≡CCH₂O 2205CHF₂O 2-naphthyl S H CH₂CH₂ CH₃O CH≡CCH₂O 2206 CF₃O 2-naphthyl S HCH₂CH₂ CH₃O CH≡CCH₂O 2207 CH₂FO 5-benzofuryl O H CH₂CH₂ CH₃O CH≡CCH₂O2208 CHF₂O 5-benzofuryl O H CH₂CH₂ CH₃O CH≡CCH₂O 2209 CF₃O 5-benzofurylO H CH₂CH₂ CH₃O CH≡CCH₂O 2210 CH₂FO 6-benzofuryl O H CH₂CH₂ CH₃OCH≡CCH₂O 2211 CHF₂O 6-benzofuryl O H CH₂CH₂ CH₃O CH≡CCH₂O 2212 CF₃O6-benzofuryl O H CH₂CH₂ CH₃O CH≡CCH₂O 2213 CH₂FO 5-benzothienyl O HCH₂CH₂ CH₃O CH≡CCH₂O 2214 CHF₂O 5-benzothienyl O H CH₂CH₂ CH₃O CH≡CCH₂O2215 CF₃O 5-benzothienyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2216 CH₂FO6-benzothienyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2217 CHF₂O 6-benzothienyl O HCH₂CH₂ CH₃O CH≡CCH₂O 2218 CF₃O 6-benzothienyl O H CH₂CH₂ CH₃O CH≡CCH₂O2219 CH₂FO 5-benzothiazolyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2220 CHF₂O5-benzothiazolyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2221 CF₃O 5-benzothiazolyl O HCH₂CH₂ CH₃O CH≡CCH₂O 2222 CH₂FO 6-benzothiazolyl O H CH₂CH₂ CH₃OCH≡CCH₂O 2223 CHF₂O 6-benzothiazolyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2224 CF₃O6-benzothiazolyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2225 CH₂FO 2-benzothiazolyl OH CH₂CH₂ CH₃O CH≡CCH₂O 2226 CHF₂O 2-benzothiazolyl O H CH₂CH₂ CH₃OCH≡CCH₂O 2227 CF₃O 2-benzothiazolyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2228 CH₂FO2-benzothienyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2229 CHF₂O 2-benzothienyl O HCH₂CH₂ CH₃O CH≡CCH₂O 2230 CF₃O 2-benzothienyl O H CH₂CH₂ CH₃O CH≡CCH₂O2231 CH₂FO 3-benzothienyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2232 CHF₂O3-benzothienyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2233 CF₃O 3-benzothienyl O HCH₂CH₂ CH₃O CH≡CCH₂O 2234 CH₂FO 2-benzofuryl O H CH₂CH₂ CH₃O CH≡CCH₂O2235 CHF₂O 2-benzofuryl O H CH₂CH₂ CH₃O CH≡CCH₂O 2236 CF₃O 2-benzofurylO H CH₂CH₂ CH₃O CH≡CCH₂O 2237 CH₂FO 3-benzofuryl O H CH₂CH₂ CH₃OCH≡CCH₂O 2238 CHF₂O 3-benzofuryl O H CH₂CH₂ CH₃O CH≡CCH₂O 2239 CF₃O3-benzofuryl O H CH₂CH₂ CH₃O CH≡CCH₂O 2240 CH₂FO benzo-1,2,3-thiazol- OH CH₂CH₂ CH₃O CH≡CCH₂O 5-yl 2241 CHF₂O benzo-1,2,3-thiazol- O H CH₂CH₂CH₃O CH≡CCH₂O 5-yl 2242 CF₃O benzo-1,2,3-thiazol- O H CH₂CH₂ CH₃OCH≡CCH₂O 5-yl 2243 CH₂FO 2-benzimidazolyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2244CHF₂O 2-benzimidazolyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2245 CF₃O2-benzimidazolyl O H CH₂CH₂ CH₃O CH≡CCH₂O 2246 CF₃S 2-thienyl O H CH₂CH₂CH₃O CH₃O 2247 CH₂FO 2-(1-methylbenzimidazolyl) O H CH₂CH₂ CH₃O CH≡CCH₂O2248 CHF₂O 2-(1-methylbenzimidazolyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2249 CF₃O2-(1-methylbenzimidazolyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2250 CH≡CCH₂O2-(5-methylthienyl) O H CH₂CH₂ CH₃O CH≡CCH₂O 2251 CH≡CCH₂O2-(5-trifluoromethyl O H CH₂CH₂ CH₃O CH₃O thienyl) 2252 CH≡CCH₂O2-(5-methylfuryl) O H CH₂CH₂ CH₃O CH₃O 2253 CH≡CCH₂O2-(5-trifluoromethyl O H CH₂CH₂ CH₃O CH₃O pyridyl) 2254 CH≡CCH₂O2-naphthyl O H CH₂CH₂ CH₃O CH₃O

Formulation examples are given below. Parts represent parts by weight.The numbers of the present compounds are represented by theabove-mentioned numbers.

Formulation Example 1

Fifty parts of each of the present compounds 1001-1478 and 2001-2254, 3parts of calcium ligninsulfonate, 2 parts of magnesium laurylsulfate and45 parts of synthetic hydrated silica are pulverized and mixed well togive wettable powders of each compound.

Formulation Example 2

Twenty parts of each of the present compounds 1001-1478 and 2001-2254and 1.5 parts of sorbitan trioleate are mixed with 28.5 parts of anaqueous solution containing 2 parts of polyvinyl alcohol, andwet-pulverized finely. To the obtained mixture, 40 parts of an aqueoussolution containing 0.05 part of xanthan gum and 0.1 part of aluminiummagnesium silicate is added and further 10 parts of propylene glycol areadded to give a flowable of each compound.

Formulation Example 3

Two parts of each of the present compounds 1001-1478 and 2001-2254, 88parts of kaolin clay and 10 parts of talc are pulverized and mixed wellto give dusts of each compound.

Formulation Example 4

Five parts of each of the present compounds 1001-1478 and 2001-2254, 14parts of polyoxyethylenestyryl phenyl ether, 6 parts of calciumdodecylbenzenesulfonate and 75 parts of xylene are mixed well to giveemulsifiable concentrates of each compound.

Formulation Example 5

Two parts of each of the present compounds 1001-1478 and 2001-2254, 1part of synthetic hydrated silica, 2 parts of calcium ligninsulfonate,30 parts of bentonite and 65 parts of kaolin clay are pulverized andmixed well, and water is added thereto and kneeded, granulated and driedto give granules of each compound.

Formulation Example 6

Ten parts of each of the present compounds 1001-1478 and 2001-2254, 35parts of white carbon (calsium silicate) containing 50% of ammoniumpolyoxyethylenealkyl ether sulfate and 55 parts of water are mixed andwet pulverized finely to give a flowable of each compound.

Next, usefulness of the present compounds for controlling plant diseasesis shown by test examples. The present compounds are represented by thenumbers referred to in the above table.

The control effect of the present compounds was evaluated by visuallyobserving the area of a lesion on a sample plant in investigation andcomparing the area of a lesion in a non-treatment district and the areaof a lesion in a district treated with the present compound.

Test Example 1

Sand loam was compacted in a plastic pot, a grape (variety: Berry A) wasseeded and grown in a green house for 40 days. The present compounds1004, 1005, 1006, 1016, 1017, 1020, 1023, 1026, 1029, 1065, 1103, 1104,1143, 1160, 1182, 1196, 1197, 1223, 1232, 1241, 1251, 1258, 1266, 1268,1271, 1274, 1281, 1282, 1305, 1320, 1371, 2077 and 2133 were formulatedinto flowables according to formulation example 6, then, diluted withwater to provide given concentration (200 ppm), and these were sprayedonto stems and leaves so as to give sufficient adhesion on the surfaceof grape leaves. After spraying, the plant was air-dried, and asuspension of zoosporangiua of Plasmopara viticola was inoculated byspraying. After inoculation, the plant was first left for one day at 23°C. under high humidity, then further left for 6 days in the green house,then the control effect was checked. As a result, the lesion areas onplants in the treatment districts using the present compounds were notmore than 10% of the lesion area of a non-treatment district.

Test Example 2

Sand loam was compacted in a plastic pot, a grape (variety: Berry A) wasseeded and grown in a green house for 40 days. The present compounds1259, 1284, 1353, 1355, 1360, 1367, 1445, 1447 and 1450 were formulatedinto flowables according to formulation example 6, then, diluted withwater to provide given concentration (50 ppm), and these were sprayedonto stems and leaves so as to give sufficient adhesion on the surfaceof grape leaves. After spraying, the plant was air-dried, and asuspension of zoosporangiua of Plasmopara viticola was inoculated byspraying. After inoculation, the plant was first left for one day at 23°C. under high humidity, then further left for 6 days in the green house,then the control effect was checked. As a result, the lesion areas onplants in the treatment districts using the present compounds were notmore than 10% of the lesion area of a non-treatment district.

Test Example 3

Sand loam was compacted in a plastic pot, a grape (variety: Berry A) wasseeded and grown in a green house for 40 days. The present compounds1354, 1357, 1358, 1364, 1388, 1392, 1429 and 2202 were formulated intoflowables according to formulation example 6, then, diluted with waterto provide given concentration (12.5 ppm), and these were sprayed ontostems and leaves so as to give sufficient adhesion on the surface ofgrape leaves. After spraying, the plant was air-dried, and a suspensionof zoosporangiua of Plasmopara viticola was inoculated by spraying.After inoculation, the plant was first left for one day at 23° C. underhigh humidity, then further left for 6 days in the green house, then thecontrol effect was checked. As a result, the lesion areas on plants inthe treatment districts using the present compounds were not more than10% of the lesion area of a non-treatment district.

Test Example 4

Sand loam was compacted in a plastic pot, a tomato (variety: Ponterosa)was seeded and grown in a green house for 20 days. The present compounds1004, 1005, 1006, 1016, 1017, 1020, 1023, 1026, 1029, 1034, 1065, 1103,1104, 1122, 1143, 1160, 1182, 1185, 1196, 1197, 1223, 1124, 1127, 1232,1241, 1251, 1258, 1259, 1268, 1269, 1274, 1281, 1282, 1284, 1299, 1320,1353, 1354, 1358, 1360, 1388, 1367, 1392, 1429, 1445, 1448, 1450, 1465,1476, 2077 and 2133 were formulated into flowables according toformulation example 6, then, diluted with water to provide givenconcentration (500 ppm), and these were sprayed onto stems and leaves soas to give sufficient adhesion on the surface of tomato leaves. Afterspraying, the plant was air-dried, and a suspension of zoosporangiua ofPhytophthora infestans was inoculated by spraying. After inoculation,the plant was first left for one day at 23° C. under high humidity, thenfurther left for 4 days in the green house, then the control effect waschecked. As a result, the lesion areas on plants in the treatmentdistricts using the present compounds were not more than 10% of thelesion area of a non-treatment district.

Industrial Applicability

The present compound has an excellent efficacy for controlling plantdiseases and is useful as an active ingredient of fungicide, especiallyagricultural and horticultural fungicide.

What is claimed is:
 1. An amide compound given by formula [I]:

wherein R¹ represents a C1-C10 haloalkyl group, C2-C10 haloalkenyl group, C3-C10 haloalkynyl group, C3-C8 halocycloalkyl group or C3-C10 alkynyl group; R² represents a hydrogen atom or C1-C3 alkyl group; X represents an oxygen atom or sulfur atom; Y represents an oxygen atom or sulfur atom; Ar represents a non heterocyclic, an aromatic group; A represents an ethylene group or trimethylene group, said ethylene group and trimethylene group may be substituted by one or more selected from halogen atom, amino group, hydroxy group, cyano group, nitro group, C1-C6 alkyl group, C3-C6 cycloalkyl group, C3-C6 cycloalkenyl group, C1-C6 alkoxy group, C1-C6 haloalkoxy group, C1-C6 alkylthio group, C1-C6 haloalkylthio group, C2-C6 (alkoxycarbonyl) group and tri(C1-C6 alkyl)silyl group; Z¹ and Z² are the same or different and represents a halogen atom, C1-C6 alkyl group, C1-C6 haloalkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C3-C6 cycloalkyl group, C1-C6 alkoxy group, C1-C6 haloalkoxy group, C2-C6 (alkoxyalkoxy) group, C4-C6 (cycloalkylalkoxy) group, C3-C6 alkenyloxy group, C3-C6 haloalkenyloxy group, C3-C6 alkynyloxy group, C3-C6 haloalkynyloxy group, C3-C6 cycloalkoxy group, C3-C6 cycloalkenyloxy group, cyano C1-C5 alkoxy group, C1-C6 alkylthio group, C1-C6 haloalkylthio group, (C1-C5 alkoxy)carbonyl group, phenoxy group, benzyloxy group, hydroxy group or cyano group, the benzene ring of said phenyl group and benzyloxy group may be substituted by one or more selected from halogen atom, C1-C6 alkyl group, C1-C6 alkoxy group, trfluoromethyl group, amino group and nitro group; and Z¹ and Z² may represents C2-C6 alkylenedioxy group together.
 2. An amide compound according to claim 1, wherein Ar is an aromatic hydrocarbyl group which may be substituted by at least one selected from halogen, amino, hydroxy, cyano, nitro, C1-C10 alkyl, C1-C10 haloalkyl, cyano C1-C9 alkyl, C2-C10 alkenyl, C2-C10 haloalkenyl, C2-C10 alkynyl, C2-C10 haloalkynyl, C3-C6 cycloalkyl, C3-C6 cycloalkenyl, C1-C10 alkoxy, C1-C10 haloalkoxy, C3-C10 alkenyloxy, C3-C10 haloalkenyloxy, C3-C10 alkynyloxy, C3-C10 haloalkynyloxy, C3-C10 cycloalkoxy, cyano C1-C9 alkoxy, C1-C10 alkylthio, C1-C10 haloalkylthio, C2-C10 (alkoxycarbonyl) and tri(C1-C6 alkyl)silyl.
 3. An amide compound according to claim 2, wherein Ar is phenyl, or naphthyl, which may be substituted by at least one selected from halogen, amino, hydroxy, cyano, nitro, C1-C10 alkyl, C1-C10 haloalkyl, cyano C1-C9 alkyl, C2-C10 alkenyl, C2-C10 haloalkenyl, C2-C10 alkynyl, C2-C10 haloalkynyl, C3-C6 cycloalkyl, C3-C6 cycloalkenyl, C1-C10 alkoxy, C1-C10 haloalkoxy, C3-C10 alkenyloxy, C3-C10 haloalkenyloxy, C3-C10 alkynyloxy, C3-C10 haloalkynyloxy, C3-C10 cycloalkoxy, cyano C1-C9 alkoxy, C1-C10 alkylthio, C1-C10 haloalkylthio, C2-C10 (alkoxycarbonyl) and tri(C1-C6 alkyl)silyl.
 4. An amide compound according to claim 2, wherein Ar is phenyl or naphthyl which may be substituted by at least one selected from halogen, amino, hydroxy, cyano, nitro, C1-C10 alkyl, C1-C10 haloalkyl, cyano C1-C9 alkyl, C2-C10 alkenyl, C2-C10 haloalkenyl, C2-C10 alkynyl, C2-C10 haloalkynyl, C3-C6 cycloalkyl, C3-C6 cycloalkenyl, C1-C10 alkoxy, C1-C10 haloalkoxy, C3-C10 alkenyloxy, C3-C10 haloalkenyloxy, C3-C10 alkynyloxy, C3-C10 haloalkynyloxy, C3-C10 cycloalkoxy, cyano C1-C9 alkoxy, C1-C10 alkylthio, C1-C10 haloalkylthio, C2-C10 (alkoxycarbonyl) and tri(C1-C6 alkyl)silyl.
 5. An amide compound according to claim 2, wherein Ar is phenyl, 4-methylphenyl, 3-methylphenyl, 4-ethylphenyl, 4-methoxyphenyl, 3-methoxyphenyl, 4-chlorophenyl, 4-trifluoromethylphenyl, 3,4-tetramethylenephenyl, 3,4-trimethylenephenyl, 3,4-dichlorophenyl, 3,4-dimethoxyphenyl or 2-naphthyl.
 6. An amide compound according to claim 1, wherein A is an ethylene group.
 7. An amide compound according to claim 1, wherein R² is a hydrogen atom.
 8. An amide compound according to claim 1, wherein both of X and Y are oxygen atoms.
 9. An amide compound according to claim 1, wherein both of Z¹ and Z² are methoxy.
 10. An amide compound according to claim 1, wherein Z¹ is methoxy and Z² is 2-propynyloxy.
 11. An amide compound according to claim 1, wherein R¹ is a fluoromethyl, difluoromethyl, trifluoromethyl or 2-propynyl.
 12. An amide compound according to claim 1, which is N-[2-(3,4-dimethoxyphenyl) ethyl]-3-difluoromethoxy-2-(4-methylphenyl)acrylamide, N-[2-(3,4-dimethoxyphenyl)ethyl]-3-difluoromethoxy-2-[2-(5,6,7,8-tetrahydronaphthalen-2-yl)]acrylamide, N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-3-difluoromethoxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide, N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-3-difluoromethoxy-2-(4-methyphenyl) acrylamide, N-[2-(3,4-dimethoxyphenyl)ethyl]-3-difluoromethoxy-2-(4-chlorophenyl)acrylamide or N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-3-difluoromethoxy-2-(4-chlorophenyl)acrylamide.
 13. A fungicide which is characterized by comprising an amide compound described in claim 1 as an active ingredient, and a carrier.
 14. A method for controlling plant diseases which is characterized by applying an effective amount of an amide compound described in claim 1 to plants. 